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/GS1 gs
BT
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[(Peter)-317.6(V)23.5(ilmos,)]TJ
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[(Ethan)-317.6(Bier)58.8(,)]TJ
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[(J.)-317.6(Lawrence)-317.6(Marsh,)]TJ
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[(and)-317.6(Arthur)-317.6(D.)-317.6(Lander)]TJ
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(3,4,5,)Tj
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[(accumulates)-282.4(as)-282.4(a)-282.4(dir)23.5(ect)-294.1(consequence)-282.3(of)-282.4(BMP)-282.4(r)23.5(eceptor)]TJ
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[(Section)-317.6(of)-317.6(Cell)-317.6(and)-317.6(Developmental)-317.6(Biology)]TJ
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[(activation)-647.1(and)-635.3(translocates)-647.1(into)-647.1(the)-647.1(nucleus)-635.3(of)-647.1(r)23.5(e)0(-)]TJ
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[(La)-317.6(Jolla,)-317.6(Califor)-23.5(nia)-317.6(92093)]TJ
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[(Padgett,)-411.8(1997;)-411.8(Raftery)-411.8(and)-411.8(Sutherland,)-411.8(1999;)-411.8(Ross)-411.8(et)]TJ
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[(Department)-317.6(of)-317.6(Mathematics)]TJ
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8.4558 0 0 8.4703 91.027 565.5138 Tm
[(Center)-317.6(for)-317.6(Complex)-317.6(Biological)-317.6(Systems)]TJ
27.7056 -1.1294 TD
[(wher)23.5(e)-329.4(i)0(t)-317.6(acts)-329.4(as)-329.4(a)-317.6(transcriptional)-329.4(cofactor)-317.6(\()]TJ
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[(W)23.5(otton)-329.4(and)]TJ
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(4)Tj
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[(Department)-317.6(of)-317.6(Developmental)-317.6(and)-317.6(Cell)-317.6(Biology)]TJ
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[(Massague,)-400(2001)]TJ
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[(\).)-400(PMad)-400(is)-400(initially)-411.8(detected)-400(in)-400(a)-400(fairly)]TJ
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(5)Tj
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[(Developmental)-317.6(Biology)-317.6(Center)]TJ
27.7056 -1.1059 TD
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[(br)11.8(oad)-305.9(a)-11.7(n)0(d)-305.9(s)-11.7(hal)-11.7(low)-305.9(p)-11.7(att)-11.7(er)-23.5(n)-317.6(duri)-11.7(ng)-305.9(m)-11.7(idb)-11.7(last)-11.7(ode)-11.7(rm)-305.8(s)-11.7(tage)-11.8(s,)]TJ
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[(University)-317.6(of)-317.6(Califor)-23.5(nia,)-317.6(Irvine)]TJ
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[(Irvine,)-317.6(Califor)-23.5(nia)-317.6(92697)]TJ
28.2353 -1.0824 TD
[(at)-282.4(the)-282.4(dorsal)-282.4(midline)-282.4(\()]TJ
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T*
(2003)Tj
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[(\).)-305.9(Establishing)-294.1(this)-305.9(peak)-294.1(of)-305.9(PMad)-294.1(staining)-305.9(r)23.5(equir)23.5(es)]TJ
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(Summary)Tj
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28.2353 -1.1059 TD
[(the)-423.5(function)-423.5(of)-423.5(at)-423.5(least)-423.5(four)-423.5(extracellular)-423.5(pr)23.5(oteins)-423.5(be-)]TJ
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[(sides)-388.2(Dpp)-388.2(itself:)-400(Sog)-388.2(\(an)-388.2(antagonist)-388.2(of)-400(BMP)-388.2(signaling)]TJ
/F2 1 Tf
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[(The)-505.9(dorsoventral)-494.1(axis)-505.9(of)-505.9(the)]TJ
/F4 1 Tf
14.7427 0 TD
(Drosophila)Tj
/F2 1 Tf
5.7171 0 TD
[(embryo)-505.9(is)]TJ
/F3 1 Tf
7.7755 -1.0824 TD
([)Tj
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[(Ferguson)-435.3(and)-447.1(Anderson,)-435.3(1992;)-447.1(Francois)-435.3(et)-447.1(al.,)-435.3(1994;)]TJ
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[(patterned)-388.2(by)-376.5(a)-388.2(gradient)-388.2(of)-388.2(bone)-376.5(morphogenetic)-388.2(pro-)]TJ
/F3 1 Tf
1 1 0 0 k
28.2353 -1.0588 TD
[(Y)82.4(u)-400(et)-400(al.,)-411.8(1996)]TJ
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[(]\),)-400(T)105.9(s)0(g)-400(\(which)-400(binds)-400(to)-400(Sog)-411.8(and)-400(Dpp)-400(to)]TJ
/F2 1 Tf
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[(tein)-529.4(\(BMP\))-517.6(ligands.)-529.4(In)-517.6(a)-529.4(process)-517.6(requiring)-529.4(at)-517.6(least)]TJ
/F3 1 Tf
28.2353 -1.0353 TD
[(form)-364.7(a)-364.7(trimeric)-364.7(inhibitory)-364.7(complex)-376.5([)]TJ
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[(Chang)-364.7(et)-364.7(al.,)-364.7(2001;)]TJ
/F2 1 Tf
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[(three)-541.2(additional)-541.2(extracellular)-541.2(proteins,)-541.2(a)-541.2(broad)-541.2(do-)]TJ
/F3 1 Tf
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28.2353 -1.0118 TD
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[(main)-670.6(of)-670.6(weak)-670.6(signaling)-658.8(forms)-670.6(and)-670.6(then)-670.6(abruptly)]TJ
/F3 1 Tf
1 1 0 0 k
28.2353 -0.9882 TD
[(Scott)-329.4(et)-329.4(al.,)-329.4(2001;)-329.4(Y)82.3(u)-329.4(et)-329.4(al.,)-329.4(1996)]TJ
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15.1185 0 TD
[(]\),)-329.4(Tld)-329.4(\(a)-329.4(pr)23.5(otease)-329.4(that)]TJ
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[(sharpens)-247.1(into)-247.1(a)-247.1(narrow)-247.1(dorsal)-247.1(midline)-247.1(peak.)-247.1(Using)-247.1(ex-)]TJ
/F3 1 Tf
28.2353 -0.9647 TD
[(cleaves)-317.6(Sog)-329.4([)]TJ
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[(Mar)23.5(ques)-317.6(et)-317.6(al.,)-329.4(1997;)-317.6(Shimell)-317.6(et)-329.4(al.,)-317.6(1991;)]TJ
/F2 1 Tf
0 0 0 1 k
-34.5154 -0.2706 TD
[(perimental)-329.4(and)-329.4(computational)-329.4(approaches,)-329.4(we)-329.4(inves-)]TJ
/F3 1 Tf
1 1 0 0 k
28.2353 -0.9412 TD
[(Shimmi)-388.2(and)-388.2(OConnor)94.1(,)-388.2(2003)]TJ
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13.2036 0 TD
[(]\),)-388.2(and)-388.2(Scw)-388.2(\(another)-388.2(BMP)]TJ
/F2 1 Tf
-41.4389 -0.2941 TD
[(tigate)-352.9(how)-352.9(the)-352.9(interactions)-352.9(of)-352.9(a)-352.9(multiprotein)-352.9(network)]TJ
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28.2353 -0.9176 TD
[(ligand)-411.8(that)-423.5(incr)23.5(eases)-411.8(the)-423.5(activity)-411.8(of)-423.5(Dpp)-411.8([)]TJ
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[(Ar)23.5(ora)-411.8(et)-423.5(al.,)]TJ
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[(create)-329.4(the)-329.4(unusual)-329.4(shape)-317.6(and)-329.4(dynamics)-329.4(of)-329.4(formation)]TJ
/F3 1 Tf
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28.2353 -0.8941 TD
[(1994;)-423.5(Nguyen)-435.3(et)-423.5(al.,)-435.3(1998)]TJ
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[(]\).)-423.5(The)-435.3(r)23.5(elationship)-423.5(between)]TJ
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[(of)-352.9(this)-341.2(gradient.)-352.9(Starting)-352.9(from)-341.2(observations)-352.9(suggest-)]TJ
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28.2353 -0.8706 TD
[(PMad)-341.2(staining)-329.4(and)-341.2(the)-341.2(expr)23.5(ession)-329.4(of)-341.2(genes)-329.4(in)-341.2(br)23.5(oader)]TJ
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-28.2353 -0.3647 TD
[(ing)-270.6(that)-270.6(receptor-mediated)-270.6(BMP)-282.4(degradation)-270.6(is)-270.6(an)-270.6(im-)]TJ
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28.2353 -0.8471 TD
[(dorsal)-352.9(patter)-23.5(ns)-352.9(pr)23.5(esumably)-341.2(r)23.5(eflects)-352.9(dif)23.5(fer)23.5(ent)-352.9(thr)23.5(eshold)]TJ
/F2 1 Tf
-28.2353 -0.3882 TD
[(portant)-517.6(driving)-529.4(force)-517.6(in)-529.4(gradient)-517.6(dynamics,)-529.4(we)-517.7(de-)]TJ
/F3 1 Tf
28.2353 -0.8235 TD
[(levels)-352.9(of)-352.9(BMP)-341.2(r)23.5(esponse)-352.9(\()]TJ
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11.7345 0 TD
[(Ashe)-352.9(et)-352.9(al.,)-341.2(2000;)-352.9(Rushlow)-352.9(et)]TJ
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[(velop)-482.4(a)-482.4(general)-482.4(model)-470.6(that)-482.4(is)-482.4(capable)-482.4(of)-482.4(capturing)]TJ
/F3 1 Tf
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28.2353 -0.8 TD
[(al.,)-317.6(2001)]TJ
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3.8947 0 TD
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-32.13 -0.4353 TD
[(both)-376.5(subtle)-364.7(aspects)-376.5(of)-364.7(gradient)-376.5(behavior)-376.5(and)-364.7(a)-376.5(level)]TJ
/F3 1 Tf
29.2353 -0.7765 TD
[(Ever)-270.6(since)-270.6(it)-270.6(became)-270.6(appar)23.5(ent)-258.8(that)-270.6(both)-270.6(Sog)-270.6(and)-270.6(T)105.9(s)0(g)]TJ
/F2 1 Tf
-29.2353 -0.4588 TD
[(of)-317.6(robustness)-317.6(that)-317.6(agrees)-317.6(with)-317.6(in)-317.6(vivo)-317.6(results.)]TJ
/F3 1 Tf
28.2353 -0.7529 TD
[(can)-270.6(act)-270.6(as)-258.8(inhibitors)-270.6(of)-270.6(BMP)-270.6(activity)94.1(,)-258.8(investigators)-270.6(have)]TJ
0 -1.2118 TD
[(found)-305.9(it)-305.9(puzzling)-294.1(that)-305.9(loss)-305.9(of)-305.9(function)-305.9(of)-294.1(either)-305.9(of)-305.9(these)]TJ
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-28.2353 -0.5059 TD
(Introduction)Tj
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28.2353 -0.7059 TD
[(molecules)-294.1(eliminates)-294.1(the)-294.1(peak)-294.1(of)-294.1(str)23.5(ong)-294.1(BMP)-294.1(signaling)]TJ
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[(activity)-458.8(at)-458.8(the)-458.8(dorsal)-470.6(midline)-458.8(\()]TJ
1 1 0 0 k
14.4399 0 TD
[(Decotto)-458.8(and)-458.8(Ferguson,)]TJ
0 0 0 1 k
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[(Patter)-23.5(ning)-376.5(of)-376.5(the)-376.5(dorsal-ventral)-364.7(axis)-376.5(of)-376.5(the)]TJ
/F5 1 Tf
20.4131 0 TD
(Drosophila)Tj
/F3 1 Tf
1 1 0 0 k
7.8222 -0.6588 TD
[(2001;)-282.4(Harland,)-294.1(2001;)-282.4(Holley)-282.3(et)-294.1(al.,)-282.3(1996;)-282.3(Ray)-294.1(and)-282.4(Whar-)]TJ
0 0 0 1 k
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[(embryo)-352.9(is)-341.2(initiated)-352.9(by)-341.2(a)-352.9(nuclear)-341.2(gradient)-352.9(of)-341.2(the)-352.9(mater-)]TJ
1 1 0 0 k
28.2353 -0.6353 TD
[(ton,)-270.6(2001)]TJ
0 0 0 1 k
4.2726 0 TD
[(\).)-270.6(How)-270.6(can)-270.6(antagonists)-282.4(be)-270.6(r)23.5(esponsible)-270.6(for)-270.6(ele-)]TJ
-32.5079 -0.6 TD
[(nally)-364.7(deposited)-364.7(transcription)-364.7(factor)-364.7(Dorsal)-364.7(\()]TJ
1 1 0 0 k
20.3866 0 TD
[(Rusch)-364.7(and)]TJ
0 0 0 1 k
7.8487 -0.6118 TD
[(vating)-376.5(the)-376.5(activity)-364.7(of)-376.5(the)-376.5(molecule)-376.5(they)-364.7(inhibit?)-376.5(T)105.9(o)-376.5(ex-)]TJ
1 1 0 0 k
-28.2353 -0.6235 TD
[(Levine,)-400(1996)]TJ
0 0 0 1 k
5.922 0 TD
[(\),)-388.2(which)-400(activates)-400(expr)23.5(ession)-388.2(of)-400(neur)23.5(oec-)]TJ
22.3133 -0.5882 TD
[(plain)-294.1(this)-294.1(seeming)-294.1(paradox,)-294.1(it)-294.1(has)-294.1(been)-294.1(suggested)-294.1(that)]TJ
-28.2353 -0.6471 TD
[(todermal)-341.2(genes)-341.2(such)-341.2(as)]TJ
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11.5727 0 TD
[(short)-341.2(gastrulation)]TJ
/F3 1 Tf
8.5164 0 TD
(\()Tj
/F5 1 Tf
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(sog)Tj
/F3 1 Tf
1.686 0 TD
0.3412 Tc
(\)\()Tj
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(Fran-)Tj
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[(Sog)-317.6(plays)-317.6(two)-329.4(r)23.5(oles)-317.6(in)-317.6(cr)23.5(eating)-317.6(the)-317.6(BMP)-329.4(activity)-317.6(gradi-)]TJ
1 1 0 0 k
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[(cois)-317.6(et)-329.4(al.,)-317.6(1994;)-329.4(Markstein)-317.6(et)-329.4(al.,)-317.6(2002)]TJ
0 0 0 1 k
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[(\))-329.4(i)0(n)-317.6(ventr)23.5(olateral)]TJ
10.3005 -0.5412 TD
[(ent.)-458.8(First,)-458.8(because)-458.8(it)-458.8(is)-447.1(pr)23.5(esent)-458.8(in)-458.8(a)-458.8(graded)-458.8(distribu-)]TJ
-28.2353 -0.6941 TD
[(r)23.5(egions)-388.2(of)-388.2(the)-376.5(embryo,)-388.2(and)-388.2(nonneur)23.5(ectodermal)-388.2(genes)]TJ
28.2353 -0.5176 TD
[(tiondif)23.5(fusing)-411.8(fr)23.5(om)-411.8(lateral)-411.8(neural)-411.8(ectoderm)-411.8(to)-411.8(form)-411.8(a)]TJ
-28.2353 -0.7176 TD
[(such)-258.8(as)]TJ
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(\()Tj
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(\),)Tj
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(tld)Tj
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[(\),)-247.1(and)]TJ
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20.7496 -0.4706 TD
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[(cellular)-247.1(blastoderm)-258.8(stage)-247.1(thr)23.5(ough)-247.1(the)-247.1(beginning)-258.8(of)-247.1(gas-)]TJ
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28.2353 -0.3765 TD
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28.2353 -0.3529 TD
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11.7012 0 TD
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[(mains:)-235.3(an)-247.1(extraembryonic)-235.3(cell)-235.3(type)-235.3(known)-247.1(as)-235.3(amnioser-)]TJ
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28.2353 -0.3294 TD
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[(ventral)-352.9(portion)-341.2(of)-352.9(the)-341.2(nonneural)-352.9(ectoderm\).)-341.2(In)-352.9(the)-341.2(dor-)]TJ
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28.2353 -0.2823 TD
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[(\).)-529.4(Second,)-541.2(Sog)-529.4(has)-541.2(been)-541.2(pr)23.5(oposed)-529.4(to)-541.2(bind)]TJ
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28.2353 -0.2588 TD
[(BMPs)-270.6(and)-270.6(carry)-270.6(them)-258.8(dorsally)94.1(,)-270.6(causing)-270.6(their)-270.6(accumula-)]TJ
-28.2353 -0.9765 TD
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28.2353 -0.2353 TD
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12.2241 0 TD
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3.4701 -0.1647 TD
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ET
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T*
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[(on)-285.7(the)-271.4(Y)-271.4(chr)14.3(omosome.)-271.4(All)-271.4(r)14.3(esulting)-271.4(female)]TJ
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6.9636 0 0 6.9755 111.4774 602.0853 Tm
[(while)-471.4(male)-471.4(embryos)-471.4(ar)14.3(e)]TJ
/F5 1 Tf
11.9683 0 TD
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6.9636 0 0 6.9755 241.0068 602.0853 Tm
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T*
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T*
[(observed)-314.3(dif)14.3(fer)14.3(ences)-314.3(between)-314.3(genotypes.)]TJ
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/F5 1 Tf
40.5756 0 TD
(sog)Tj
/F3 1 Tf
1.9801 0 TD
[(gene)-294.1(dosage)-294.1(have)-294.1(large)]TJ
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[(ar)23.5(e)-305.9(expr)23.5(essed)-305.9(at)-305.9(ectopic)-317.6(locations,)-305.9(studies)-305.9(that)-305.9(further)]TJ
28.2353 -0.0235 TD
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[(demonstrate)-247.1(a)-258.8(r)23.5(equir)23.5(ement)-247.1(for)-258.8(Tld)-247.1(in)-247.1(this)-258.8(pr)23.5(ocess)-247.1(\()]TJ
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23.0962 0 TD
(Ashe)Tj
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5.1391 -0.0471 TD
[(blastoderm.)-458.8(In)-458.8(wild-type)-458.8(females,)-470.6(this)-458.8(stripe)-458.8(is)]TJ
/F6 1 Tf
22.8046 0 TD
(w)Tj
/F3 1 Tf
1 0 TD
(56)Tj
1 1 0 0 k
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[(and)-364.7(Levine,)-352.9(1999)]TJ
0 0 0 1 k
7.9807 0 TD
[(\).)-364.7(Thus,)-352.9(the)-364.7(transport)-352.9(function)-364.7(of)-352.9(Sog)]TJ
20.2546 -0.0706 TD
[(cells)-282.3(acr)23.5(oss)-282.4(\()]TJ
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6.0272 0 TD
[(Figur)23.5(e)-282.4(1)]TJ
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[(A\),)-282.4(wher)23.5(eas)-282.4(in)]TJ
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(/+)Tj
8.4558 0 0 8.4703 448.4446 521.3688 Tm
[(females,)-282.4(it)-282.4(is)]TJ
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28.2353 -0.0941 TD
[(appr)23.5(oximately)-435.3(twice)-423.5(as)-435.3(wide)-435.3(\(1013)-435.3(cells;)]TJ
1 1 0 0 k
20.2587 0 TD
[(Figur)23.5(e)-435.3(1)]TJ
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(B\).)Tj
-52.3708 -1.1176 TD
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28.2353 -0.1176 TD
[(Conversely)94.1(,)-352.9(when)-341.2(the)]TJ
/F5 1 Tf
10.327 0 TD
(sog)Tj
/F3 1 Tf
2.0389 0 TD
[(dose)-352.9(is)-341.2(incr)23.5(eased)-352.9(\(two)-352.9(cop-)]TJ
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[(form)-411.8(by)-411.8(Sog)-400(cleavage)-411.8(\()]TJ
1 1 0 0 k
11.1403 0 TD
[(Ashe,)-411.8(2002;)-411.8(Eldar)-400(et)-411.8(al.,)-411.8(2002;)]TJ
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17.095 -0.1412 TD
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/F3 1 Tf
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[(in)-329.4(males)-329.4(or)-329.4(thr)23.5(ee)-329.4(in)-341.2(females\),)-329.4(PMad)-329.4(staining)]TJ
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[(Meinhar)23.5(dt)-705.9(and)-694.1(Roth,)-705.9(2002;)-705.9(Shimmi)-694.1(and)-705.9(OConnor)94.1(,)]TJ
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28.2353 -0.1647 TD
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(2003)Tj
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[(\).)-576.5(In)-576.5(the)-576.5(case)-576.5(of)-564.7(T)105.9(sg,)-576.5(genetic)-576.5(and)-576.5(biochemical)]TJ
26.0113 -0.1882 TD
[(points)-258.8(along)-247.1(the)-258.8(midline)-247.1(\()]TJ
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[(Figur)23.5(e)-258.8(1)]TJ
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[(C\).)-258.8(These)-247.1(changes)-258.8(ar)23.5(e)]TJ
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28.2353 -0.2118 TD
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-28.2353 -1 TD
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28.2353 -0.2353 TD
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[(heter)23.5(ozygous)-400(embryos)]TJ
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28.2353 -0.2588 TD
(\()Tj
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[(Biehs)-458.8(et)-447.1(al.,)-458.8(1996)]TJ
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[(Scott)-317.6(et)-317.6(al.,)-317.6(2001;)-317.6(Shimmi)-317.6(and)-317.6(OConnor)94.1(,)-317.6(2003)]TJ
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[(dosage,)-270.6(is)-258.8(not)-270.6(a)-270.6(characteristic)]TJ
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[(PMad)-529.4(activation)-529.4(and)-517.6(expr)23.5(ession)-529.4(of)-529.4(dosage-sensitive)]TJ
T*
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T*
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T*
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[(Figur)23.5(e)-329.4(6)]TJ
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[(the)-314.3(Dorsal)-314.3(Midline)]TJ
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[(large)-470.6(as)-482.4(that)-470.6(observed)-482.4(in)-470.6(vivo)-482.4(\()]TJ
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[(Figur)23.5(e)-470.6(1)]TJ
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[(For)-442.9(many)-442.9(parameter)-442.9(sets,)-442.9(an)-442.8(early)-442.9(phase)-442.8(with)-442.8(low)-442.8(level)-442.9(of)-442.9(BMP)]TJ
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[(looked)-388.2(at)-388.2(over)-388.2(a)-388.2(wide)-376.5(range)-388.2(of)-388.2(parameter)-388.2(values)-388.2(\(see)]TJ
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[(activity)-428.6(br)14.3(oadly)-442.9(distributed)-428.6(acr)14.3(oss)-428.6(the)-442.9(entir)14.3(e)-428.6(dorsal)-428.6(r)14.3(egion)-442.8(is)-428.6(fol-)]TJ
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[(exert)-300(opposing)-300(gene)-300(dosage)-300(ef)14.3(fects)-300(that)-300(appr)14.3(oximately)-300(cancel)]TJ
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T*
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[(embryos)-314.3(\()]TJ
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28.2353 -1.2353 TD
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[(\),)-470.6(but)-482.4(the)-470.6(model)-470.6(ex-)]TJ
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[(\).)-294.1(The)-282.4(data)-294.1(in)]TJ
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[(Figur)23.5(es)-294.1(7)]TJ
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28.2353 -1.2353 TD
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[(ing)-294.1(because,)-294.1(individually)94.1(,)]TJ
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5.4008 -1.2353 TD
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31.952 0 TD
[(Balemans)-517.6(and)-517.6(V)58.8(a)0(n)-517.6(Hul,)]TJ
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[(2002;)-317.6(Kawano)-317.6(and)-317.6(Kypta,)-317.6(2003)]TJ
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8.4558 0 0 8.4703 185.5434 72.7445 Tm
[(embryo)-294.1(is)-294.1(due)-294.1(to)-294.1(a)]TJ
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T*
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[(driven)-305.9(by)-305.9(a)-305.9(morphogen)-305.9(gradient)-305.9(that)-305.9(is)-305.9(distinctive)-305.9(in)-305.9(at)]TJ
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[(Supplemental)-411.8(Data)]TJ
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[(unusual)-270.6(pr)23.5(ofile,)-270.6(with)-282.4(a)-270.6(sharp)-270.6(peak)-270.6(at)-282.4(the)-270.6(dorsal)-270.6(midline;)-2811(could)-317.6(be)-317.7(captur)23.5(ed.)-305.9(Inter)23.5(estingly)94.1(,)-317.7(a)-317.6(gr)23.5(eat)-317.7(many)-305.9(of)-317.6(those)]TJ
28.2353 -1.2235 TD
[(behaviors)-247.1(emerge)-247.1(fr)23.5(om)-247.1(a)-247.1(model)-258.8(in)-247.1(which)-247.1(a)-247.1(single)-247.1(ligand)]TJ
-28.2353 0 TD
[(and)-294.1(it)-294.1(r)23.5(elies)-294.1(upon)-294.1(the)-282.4(activities)-294.1(of)-294.1(at)-294.1(least)-294.1(thr)23.5(ee)-294.1(nonsig-)]TJ
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[(naling,)-364.7(secr)23.5(eted)-352.9(pr)23.5(oteins)-364.7(\(Sog,)-352.9(T)105.9(sg,)-364.7(and)-352.9(Tld\).)-364.7(The)-352.9(goal)-2821.6(\(e.g.,)-317.7(Dpp)-305.9(or)-317.6(a)-317.7(Dpp/Scw)-305.9(heter)23.5(odimer\))-317.6(dif)23.5(fuses)-305.9(fr)23.5(eely)94.1(,)-317.6(i)0(s)]TJ
28.2353 -1.2235 TD
[(degraded)-305.9(by)-317.6(r)23.5(eceptors,)-305.9(forms)-305.9(a)-317.6(complex)-305.9(with)-317.6(Sog)-305.9(and)]TJ
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[(of)-247.1(the)-247.1(pr)23.5(esent)-247.1(study)-247.1(was)-247.1(to)-247.1(r)23.5(eveal)-247.1(how)-247.1(these)-247.1(character-)]TJ
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[(isticsdynamics,)-505.9(shape,)-505.9(and)-517.6(pr)23.5(otein-pr)23.5(otein)-505.9(interac-)-2813(T)105.9(sg,)-658.8(and)-670.6(is)-658.8(r)23.5(eleased)-658.8(fr)23.5(om)-670.6(that)-658.8(complex)-670.6(when)-658.8(Tld)]TJ
28.2353 -1.2235 TD
[(cleaves)-341.2(Sog.)-329.4(These)-341.2(behaviors)-341.2(include)-329.4(rapid)-341.2(dynamics,)]TJ
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[(tionsdepend)-317.6(on)-317.6(each)-317.6(other)94.1(.)]TJ
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[(W)23.5(e)-388.2(began)-388.2(by)-388.2(showing)-400(that)-388.2(r)23.5(obustness)-388.2(with)-388.2(r)23.5(espect)-2829.4(formation)-376.5(of)-388.2(a)-376.5(b)0(r)23.5(oad)-388.2(domain)-376.5(of)-376.5(weak)-388.2(dorsal)-376.5(signaling)]TJ
27.2353 -1.2235 TD
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[(to)-341.2(variations)-352.9(in)-341.2(the)-341.2(expr)23.5(ession)-341.2(of)-352.9(single)-341.2(genes)-341.2(is)-352.9(not)-341.2(a)]TJ
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[(characteristic)-411.8(of)-400(this)-411.8(system)-400(\()]TJ
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14.0735 0 TD
[(Figur)23.5(e)-411.8(1)]TJ
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[(\).)-400(This)-411.8(is)-411.8(an)-400(im-)-2812(narr)23.5(owing)-305.9(or)-317.6(br)23.5(oadening)-305.9(when)]TJ
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[(dosage)-305.9(is)-317.6(either)-305.9(in-)]TJ
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[(cr)23.5(eased)-435.3(or)-435.3(decr)23.5(eased,)-435.3(r)23.5(espectively)-423.5(\()]TJ
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[(Figur)23.5(es)-435.3(5)-435.3(and)-435.3(6)]TJ
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[(portant)-400(observation,)-400(given)-400(that)-400(considerable)-400(attention)]TJ
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28.2353 -1.2235 TD
[(of)-447.1(Sog,)-458.8(T)105.9(sg,)-447.1(and)-458.8(Tld)-447.1(and)-447.1(ar)23.5(e)-458.8(also)-447.1(highly)-458.8(sensitive)-447.1(to)]TJ
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[(gen-patter)-23.5(ning)-647.1(systems)-658.8(\()]TJ
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[(Eldar)-647.1(et)-647.1(al.,)-658.8(2003;)-647.1(Houch-)]TJ
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[(mandzadeh)-423.5(et)-423.5(al.,)-411.8(2002;)-423.5(von)-423.5(Dassow)-423.5(et)-411.8(al.,)-423.5(2000)]TJ
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2.3859 0 TD
[(dosage)-564.7(\(in)-552.9(agr)23.5(eement)-552.9(with)]TJ
1 1 0 0 k
13.593 0 TD
[(Dorfman)-564.7(and)-552.9(Shilo,)]TJ
-15.979 -1.2235 TD
[(2001;)-305.9(Rusch)-294.1(and)-305.9(Levine,)-305.9(1997;)-294.1(Sutherland)-305.9(et)-294.1(al.,)-305.9(2003)]TJ
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24.8668 0 TD
(\).)Tj
-53.1021 0 TD
[(well)-282.4(as)-294.1(biological)-282.4(signaling)-294.1(in)-282.4(general)-294.1(\()]TJ
1 1 0 0 k
17.7394 0 TD
[(Alon)-282.4(et)-294.1(al.,)-282.3(1999;)]TJ
-17.7394 -1.2235 TD
[(Mor)23.5(ohashi)-423.5(et)-423.5(al.,)-423.5(2002)]TJ
0 0 0 1 k
10.6041 0 TD
[(\).)-423.5(The)-423.5(fact)-423.5(that)]TJ
/F5 1 Tf
7.5291 0 TD
(sog)Tj
/F3 1 Tf
6.2672 0 0 5.5804 254.1348 550.0676 Tm
()Tj
/F5 1 Tf
0.6 0 TD
(/+)Tj
/F3 1 Tf
8.4558 0 0 8.4703 267.4429 546.9785 Tm
[(embryos)-2822.3(Inter)23.5(estingly)94.1(,)-352.9(highly)-352.9(localized)-352.9(expr)23.5(ession)-364.7(of)-352.9(Tld)-352.9(and)-352.9(an)]TJ
6.8423 -1.2235 TD
[(absolute)-341.2(dependence)-341.2(of)-352.9(Sog)-341.2(cleavage)-341.2(on)-341.2(Dpp)-352.9(ar)23.5(e)-341.2(not)]TJ
-28.2353 0 TD
[(eventually)-376.5(develop)-376.5(normally)-376.5(underscor)23.5(es)-376.5(the)-376.5(ability)-376.5(of)]TJ
0 -1.2235 TD
[(embryos)-317.6(to)-317.6(compensate)-317.6(at)-329.4(later)-317.6(stages)-317.6(for)-317.6(early)-317.6(err)23.5(ors)-2824.9(essential)-294.1(\(data)-282.4(not)-294.1(shown\).)-294.1(Also)-282.4(not)-294.1(critical)-294.1(is)-282.4(the)-294.1(or)23.5(der)]TJ
28.2353 -1.2235 TD
[(of)-317.7(assembly)-317.6(of)-317.7(Dpp-Sog-Tld)-317.6(complexes.)]TJ
-28.2353 0 TD
(\(cf.)Tj
1 1 0 0 k
1.8152 0 TD
[(Houchmandzadeh)-400(et)-388.2(al.,)-400(2002)]TJ
0 0 0 1 k
14.0813 0 TD
[(\).)-388.2(It)-400(is)-388.2(not)-388.2(clear)-400(why)]TJ
-15.8965 -1.2235 TD
[(marked)-341.2(ef)23.5(fects)-341.2(of)]TJ
/F5 1 Tf
8.54 0 TD
(sog)Tj
/F3 1 Tf
2.0154 0 TD
[(heter)23.5(ozygosity)-341.2(wer)23.5(e)-341.2(not)-341.2(seen)-341.2(in)-3819.2(Although)-435.3(the)-423.5(ability)-435.3(of)-423.5(the)-435.3(model)-423.5(to)-435.3(form)-423.5(a)-435.3(midline)]TJ
17.6799 -1.2235 TD
[(peak)-447.1(of)-447.1(BMP)-447.1(activity)-435.3(exemplifies)-447.1(the)-447.1(Sog/Tld-depen-)]TJ
-28.2353 0 TD
[(similar)-258.8(experiments)-258.8(by)]TJ
1 1 0 0 k
10.6315 0 TD
[(Eldar)-258.8(et)-258.8(al.)-258.8(\(2002\))]TJ
0 0 0 1 k
7.9105 0 TD
[(;)-258.8(this)-258.8(may)-258.8(have)]TJ
-18.542 -1.2235 TD
[(been)-235.3(r)23.5(elated)-235.3(to)-247.1(their)-235.3(inability)-235.3(to)-235.3(genotype)-247.1(individual)-235.3(em-)-2826.9(dent)-258.8(shuttling)-270.6(pr)23.5(oposed)-258.8(by)-258.8(others)-258.8(\()]TJ
1 1 0 0 k
45.2427 0 TD
[(Holley)-270.6(et)-258.8(al.,)-258.8(1996;)]TJ
-17.0074 -1.2235 TD
[(Ross)-494.1(et)-494.1(al.,)-494.1(2001;)-482.3(Shimmi)-494.1(and)-494.1(OConnor)94.1(,)-494.1(2003)]TJ
0 0 0 1 k
22.565 0 TD
[(\),)-494.1(that)]TJ
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[(bryos,)-447.1(or)-435.3(to)-447.1(a)-447.1(lower)-435.3(sensitivity)-447.1(of)-447.1(PMad)-435.3(staining.)-447.1(W)23.5(e)]TJ
0 -1.2235 TD
[(note)-423.5(that)-411.8(r)23.5(ecent)-423.5(observations)-411.8(on)-423.5(accumulation)-411.8(of)-423.5(the)-2822.4(mechanism)-258.8(does)-270.6(not)-258.8(give)-258.8(a)-258.8(complete)-270.6(pictur)23.5(e)-258.8(o)0(f)-258.8(events.)]TJ
28.2353 -1.2235 TD
[(For)-305.9(one)-317.7(thing,)-305.9(the)-305.9(abrupt)-317.6(onset)-305.9(of)-305.9(midline)-317.6(peak)-305.9(gr)23.5(owth)]TJ
-28.2353 0 TD
[(co-smad)-458.8(Medea)-458.8(in)-458.8(wild-type)-470.6(and)-458.8(pr)23.5(esumptive)]TJ
/F5 1 Tf
22.5802 0 TD
(sog)Tj
/F3 1 Tf
6.2672 0 0 5.5804 291.7378 456.7953 Tm
()Tj
/F5 1 Tf
0.6 0 TD
(/+)Tj
/F3 1 Tf
8.4558 0 0 8.4703 86.5476 443.3425 Tm
[(embryos)-435.3(\()]TJ
1 1 0 0 k
4.7333 0 TD
[(Sutherland)-435.3(et)-435.3(al.,)-435.3(2003)]TJ
0 0 0 1 k
10.7909 0 TD
[(\))-447.1(look)-435.3(very)-435.3(similar)-435.3(to)-2824.1(after)-352.9(a)-341.2(substantial)-352.9(plateau)-352.9(phase)-352.9(r)23.5(eflects)-341.2(a)-352.9(BMP-cata-)]TJ
12.7111 -1.2235 TD
[(lyzed)-258.8(chain)-270.6(r)23.5(eaction)-258.8(of)-270.6(Sog)-258.8(destruction)-258.8(that)-270.6(is)-258.8(indepen-)]TJ
-28.2353 0 TD
[(our)-282.4(observations)-294.1(on)-282.4(PMad)-294.1(in)-282.4(embryos)-282.4(of)-294.1(unambiguous)]TJ
0 -1.2235 TD
[(genotype)-317.6(\()]TJ
1 1 0 0 k
4.9307 0 TD
[(Figur)23.5(es)-317.6(1)]TJ
0 0 0 1 k
4.2781 0 TD
[(A)-317.6(and)-317.6(1B\).)-14167.2(dent)-529.4(of)-529.4(BMP)-529.4(transport)-541.2(per)-529.4(se.)-529.4(Second,)-529.4(calculations)]TJ
19.0265 -1.2235 TD
[(show)-247.1(that)-235.3(any)-247.1(soluble)-247.1(inhibitor)-235.3(has)-247.1(the)-247.1(ability)-235.3(to)-247.1(expand)]TJ
-27.2353 0 TD
[(W)23.5(e)-505.9(next)-494.1(examined)-505.9(the)-505.9(dif)23.5(fusibility)-505.9(of)-494.1(BMPs)-505.9(in)-505.9(the)]TJ
-1 -1.2235 TD
[(embryo)-305.9(in)-305.9(the)-294.1(pr)23.5(esence)-305.9(and)-305.9(absence)-305.9(of)-305.9(Sog)-294.1(\()]TJ
1 1 0 0 k
21.148 0 TD
[(Figur)23.5(es)-305.9(2)]TJ
0 0 0 1 k
7.0873 0 TD
[(the)-329.4(range)-329.4(of)-329.4(action)-329.4(of)-329.4(a)-329.4(morphogen)-329.4(simply)-329.4(by)-329.4(pr)23.5(otect-)]TJ
0 -1.2235 TD
[(ing)-352.9(it)-352.9(fr)23.5(om)-352.9(r)23.5(eceptor)58.8(-mediated)-352.9(destruction.)-352.9(Indeed,)-352.9(this)]TJ
1 1 0 0 k
-28.2353 0 TD
[(and)-294.1(3)]TJ
0 0 0 1 k
2.5911 0 TD
[(\).)-294.1(Recently)94.1(,)]TJ
1 1 0 0 k
5.3554 0 TD
[(Eldar)-294.1(et)-294.1(al.)-294.1(\(2002\))]TJ
0 0 0 1 k
8.2987 0 TD
[(asserted)-294.1(that)-294.1(BMPs)]TJ
-16.2452 -1.2235 TD
[(ar)23.5(e)-364.7(e)0(f)23.5(fectively)-376.5(indif)23.5(fusible)-364.7(in)-376.5(the)-364.7(embryo,)-376.5(except)-364.7(when)-2819.6(ef)23.5(fect)-258.8(alone)-247.1(could)-258.8(underlie)-258.8(some)-247.1(of)-258.8(the)-258.8(gr)23.5(eater)-247.1(range)-258.8(of)]TJ
28.2353 -1.2235 TD
[(action)-258.8(of)-247.1(ectopically)-258.8(expr)23.5(essed)-247.1(Dpp)-258.8(in)-247.1(wild-type)-258.8(versus)]TJ
-28.2353 0 TD
[(complexed)-517.6(with)-505.9(Sog.)-517.6(In)-517.6(contrast,)-517.6(by)-505.9(examining)-517.6(em-)]TJ
0 -1.2235 TD
[(bryos)-305.9(in)-317.6(which)-305.9(Dpp)-317.6(was)-305.9(ectopically)-317.6(expr)23.5(essed,)-305.9(we)-317.6(ob-)]TJ
/F5 1 Tf
28.2353 0 TD
(sog)Tj
/F3 1 Tf
6.2672 0 0 5.5804 339.5561 363.5229 Tm
()Tj
8.4558 0 0 8.4703 346.0024 360.4337 Tm
(embryos.)Tj
-1.4484 -1.2235 TD
[(At)-258.8(least)-258.8(one)-247.1(featur)23.5(e)-258.8(o)0(f)-258.8(the)-258.8(model)-258.8(that)-247.1(does)-258.8(not)-258.8(match)]TJ
-29.2353 0 TD
[(served)-282.3(that)-270.6(the)-282.4(range)-270.6(of)-282.4(Dpp)-282.4(action)-270.6(was)-282.4(r)23.5(educed)-270.6(in)-282.4(the)]TJ
0 -1.2235 TD
[(absence)-505.9(of)-494.1(Sog,)-505.9(but)-494.1(still)-505.9(substantial,)-494.1(and)-505.9(consistent)-2814.4(in)-517.7(vivo)-505.9(observations,)-517.6(even)-505.9(when)-517.6(investigated)-505.9(over)-517.7(a)]TJ
28.2353 -1.2235 TD
[(wide)-458.8(range)-458.8(of)-458.8(parameter)-447.1(values,)-458.8(is)-458.8(the)-458.8(magnitude)-458.8(of)]TJ
-28.2353 0 TD
[(with)-588.2(unhinder)23.5(ed)-588.2(dif)23.5(fusion.)-588.2(By)-588.2(observing)-588.2(the)-588.2(rate)-588.2(at)]TJ
0 -1.2235 TD
[(which)-329.4(continuous)-329.4(ectopic)-329.4(Dpp)-341.2(expr)23.5(ession)-329.4(gave)-329.4(rise)-329.4(to)-2821.2(the)-376.5(ef)23.5(fect)-376.5(of)]TJ
/F5 1 Tf
34.3549 0 TD
(sog)Tj
/F3 1 Tf
2.0625 0 TD
[(heter)23.5(ozygosity)-376.5(on)-376.5(PMad)-388.2(peak)-376.5(width.)]TJ
1 1 0 0 k
-8.1821 -1.2235 TD
-0.0235 Tc
[(Fi)-11.7(gur)23.6(e)-258.8(1)]TJ
0 0 0 1 k
3.7944 0 TD
[(su)-11.7(gge)-11.7(sts)-247(a)-258.8(nea)-11.7(r)-247(d)0(o)-11.7(ubli)-11.7(ng)-247(o)-11.7(f)-247(pe)-11.7(ak)-247(wi)-11.7(dth)-11.7(,)-247(w)0(h)-11.7(e)0(r)23.6(e)0(a)-11.7(s)]TJ
-32.0297 0 TD
0 Tc
[(an)-388.2(unchanging)-388.2(r)23.5(esponse)-388.2(pr)23.5(ofile,)-388.2(we)-388.2(wer)23.5(e)-388.2(also)-388.2(able)-388.2(to)]TJ
0 -1.2235 TD
[(infer)-482.4(that)-482.4(Dpp)-482.4(must)-482.4(undergo)-482.4(rapid)-482.4(degradation,)-482.3(pr)23.5(e-)-2822.3(calculations)-294.1(pr)23.5(edict)-294.1(a)-294.1(mor)23.5(e)-305.9(modest)-294.1(incr)23.5(ease)-294.1(\()]TJ
1 1 0 0 k
49.3382 0 TD
[(Figur)23.5(e)-294.1(6)]TJ
0 0 0 1 k
3.7356 0 TD
(\).)Tj
-24.8385 -1.2235 TD
[(Even)-447.1(accounting)-435.3(for)-447.1(the)-447.1(nonlinearity)-435.3(of)-447.1(immunohisto-)]TJ
-28.2353 0 TD
[(sumably)-400(thr)23.5(ough)-400(r)23.5(eceptor)58.8(-dependent)-411.8(means.)-400(In)-400(these)]TJ
0 -1.2235 TD
[(experiments,)-329.4(levels)-341.2(of)-329.4(expr)23.5(ession)-341.2(of)-329.4(ectopic)-341.2(Dpp)-329.4(wer)23.5(e)-2820.2(chemistry)-447.1(and)-447.1(the)-447.1(fact)-447.1(that)-447.1(PMad)-447.1(may)-447.1(not)-447.1(be)-447.1(an)-447.1(in-)]TJ
28.2353 -1.2235 TD
[(stantaneous)-329.4(r)23.5(ead-out)-329.4(of)-329.4(BMP)-341.2(r)23.5(eceptor)-329.4(occupancy)94.1(,)-329.4(the)]TJ
-28.2353 0 TD
[(not)-235.3(high)-235.3(\(2.5-fold)-235.3(above)-235.3(normal)-247.1(when)-235.3(two)-235.3(copies)-235.3(of)-235.3(st2-)]TJ
/F5 1 Tf
0 -1.2235 TD
(dpp)Tj
/F3 1 Tf
2.4212 0 TD
[(wer)23.5(e)-588.2(p)0(r)23.5(esent,)-576.5(as)-588.2(in)]TJ
1 1 0 0 k
10.2051 0 TD
[(Figur)23.5(e)-588.2(2)]TJ
0 0 0 1 k
4.0297 0 TD
[(;)-576.5(p)0(r)23.5(esumably)-588.2(only)-2824(data)-317.6(suggest)-317.6(that)-317.6(other)-305.9(pr)23.5(ocesses,)-317.7(not)-317.6(captur)23.5(ed)-317.6(in)-317.6(the)]TJ
11.5792 -1.2235 TD
[(simple)-376.5(model,)-364.7(r)23.5(egulate)-376.5(the)-376.5(shape)-376.5(of)-364.7(PMad)-376.5(peaks.)-376.5(For)]TJ
-28.2353 0 TD
[(slightly)-376.5(above)-364.7(normal)-376.5(when)-364.7(one)-376.5(copy)-364.7(was)-376.5(pr)23.5(esent,)-364.7(as)]TJ
0 -1.2118 TD
(in)Tj
1 1 0 0 k
1.1915 0 TD
[(Figur)23.5(e)-364.7(3)]TJ
0 0 0 1 k
3.8062 0 TD
[(\).)-376.5(It)-376.5(should)-364.7(also)-376.5(be)-376.5(noted)-376.5(that)-364.7(these)-376.5(r)23.5(esults)-2822.9(example,)-411.8(it)-411.8(might)-411.8(be)-411.8(necessary)-400(to)-411.8(include)-411.8(the)-411.8(ef)23.5(fects)]TJ
23.2376 -1.2118 TD
[(of)-329.4(a)-329.4(novel)-329.4(truncated)-329.4(form)-317.6(of)-329.4(Sog)-329.4(that)-329.4(pr)23.5(omotes,)-329.4(rather)]TJ
-28.2353 0 TD
[(cannot)-329.4(be)-329.4(accounted)-341.2(for)-329.4(by)-329.4(the)-329.4(fact)-329.4(that)-341.2(Eve2)-329.4(expr)23.5(es-)]TJ
0 -1.2118 TD
[(sion)-329.4(is)-329.4(weakly)-329.4(observed)-329.4(in)-341.2(a)-329.4(wider)-329.4(domain)-329.4(at)-329.4(its)-329.4(onset)-2827.4(than)-317.6(inhibits,)-317.7(BMP)-317.6(signaling)-317.6(\()]TJ
1 1 0 0 k
41.8249 0 TD
[(Y)82.4(u)-317.6(et)-317.6(al.,)-317.6(2004)]TJ
0 0 0 1 k
6.5586 0 TD
(\).)Tj
-19.1482 -1.2118 TD
[(One)-482.4(pr)23.5(ocess)-470.6(that)-482.3(seems)-482.4(especially)-482.3(likely)-470.6(to)-482.4(shape)]TJ
-29.2353 0 TD
(\()Tj
1 1 0 0 k
0.278 0 TD
[(Small)-282.4(et)-282.4(al.,)-282.3(1992)]TJ
0 0 0 1 k
7.8691 0 TD
[(\),)-282.4(for)-282.4(several)-294.1(r)23.5(easons.)-282.4(First,)-282.4(the)-282.4(rapid-)]TJ
-8.1471 -1.2118 TD
[(ity)-258.8(with)-258.8(which)-258.8(early)-258.8(PMad)-258.8(signals)-247.1(ar)23.5(e)-258.8(lost)-258.8(in)-258.8(the)-258.8(embryo)-2821.3(PMad)-317.6(peaks)-329.4(is)-317.7(a)-329.4(BMP-driven,)-317.6(transcription-dependent)]TJ
28.2353 -1.2118 TD
[(feedback)-470.6(loop)-470.6(that)-470.6(has)-470.6(very)-470.6(r)23.5(ecently)-470.6(been)-470.6(shown)-470.6(to)]TJ
-28.2353 0 TD
[(\(e.g.,)-305.9(in)-305.9(lateral)-305.9(portions)-317.6(of)-305.9(the)-305.9(dorsal)-305.9(ectoderm\))-305.9(implies)]TJ
0 -1.2118 TD
[(that)-305.9(ther)23.5(e)-317.6(should)-305.9(be)-305.9(little)-305.9(per)23.5(durance)-317.6(of)-305.9(BMP)-305.9(signaling)-2822.7(markedly)-376.5(amplify)-364.7(high)-376.5(and)-364.7(depr)23.5(ess)-376.5(low)-376.5(levels)-364.7(of)-376.5(BMP)]TJ
28.2353 -1.2118 TD
[(signaling)-400(in)-400(the)]TJ
/F5 1 Tf
7.61 0 TD
(Drosophila)Tj
/F3 1 Tf
5.4128 0 TD
[(embryo)-400(\()]TJ
1 1 0 0 k
4.179 0 TD
[(W)35.3(ang)-400(and)-400(Fergu-)]TJ
0 0 0 1 k
-45.4371 0 TD
[(over)-435.3(the)-435.3(time)-435.3(course)-435.3(of)-435.3(the)-447.1(experiments)-435.3(in)]TJ
1 1 0 0 k
21.0181 0 TD
[(Figur)23.5(es)-435.3(2)]TJ
-21.0181 -1.2118 TD
[(and)-447.1(3)]TJ
0 0 0 1 k
2.7441 0 TD
[(.)-458.8(Second,)-447.1(the)-447.1(rapidity)-447.1(of)-458.8(Dpp)-447.1(degradation)-447.1(sug-)]TJ
1 1 0 0 k
25.4912 0 TD
[(son,)-423.5(2005)]TJ
0 0 0 1 k
4.6115 0 TD
[(\).)-423.5(Such)-423.5(feedback)-423.5(could)-435.3(not)-423.5(only)-423.5(modify)-423.5(the)]TJ
-4.6115 -1.2118 TD
[(shapes)-294.1(of)-294.1(PMad)-294.1(peaks,)-282.3(but)-294.1(also)-294.1(potentially)-294.1(explain)-294.1(an-)]TJ
-28.2353 0 TD
[(gests)-505.9(that)-494.1(ther)23.5(e)-505.9(should)-505.9(be)-494.1(little)-505.9(per)23.5(durance)-494.1(of)-505.9(Dpp-)]TJ
0 -1.2118 TD
[(r)23.5(eceptor)-447.1(complexes.)-447.1(Finally)94.1(,)-447.1(i)0(t)-447.1(i)0(s)-447.1(clear)-447.1(that)-447.1(the)-447.1(range)-2822.4(other)-447.1(peculiarity)-458.8(of)-447.1(the)-458.8(model,)-447.1(which)-458.8(is)-447.1(that)-458.8(its)-447.1(peak)]TJ
28.2353 -1.2118 TD
[(heights)-341.2(and)-352.9(widths)-341.2(best)-352.9(fit)-341.2(mutant)-352.9(data)-341.2(when)-352.9(they)-341.2(ar)23.5(e)]TJ
-28.2353 0 TD
[(of)-552.9(Dpp)-552.9(action)-541.2(in)]TJ
1 1 0 0 k
8.72 0 TD
[(Figur)23.5(e)-552.9(2)]TJ
0 0 0 1 k
3.9944 0 TD
[(D)-552.9(extends)-541.2(mor)23.5(e)-552.9(than)-552.9(two)]TJ
/F5 1 Tf
-12.7144 -1.2118 TD
(eve)Tj
/F3 1 Tf
2.0944 0 TD
[(stripes)-482.4(past)]TJ
/F5 1 Tf
6.1147 0 TD
(eve)Tj
/F3 1 Tf
1.612 0 TD
[(-st2)-482.4(and)-482.4(continues)-482.4(to)-482.4(build)-482.4(pr)23.5(o-)-2819(looked)-458.8(at)-458.8(up)-458.8(to)-458.8(the)-447.1(3045)-458.8(min)-458.8(period,)-458.8(but)-458.8(not)-458.8(much)]TJ
18.4142 -1.2118 TD
[(later)-364.7(\(i.e.,)-364.7(not)-364.7(in)-364.7(the)-364.7(mathematical)-364.7(steady)-364.7(state\).)-364.7(Since)]TJ
-28.2353 0 TD
[(gr)23.5(essively)-341.2(even)-329.4(after)]TJ
/F5 1 Tf
9.9202 0 TD
(eve)Tj
/F3 1 Tf
1.612 0 TD
[(-st2)-329.4(has)-341.2(fully)-329.4(r)23.5(efined)-341.2(to)-329.4(a)-341.2(nar-)]TJ
-11.5322 -1.2118 TD
[(r)23.5(o)0(w)-317.6(stripe.)-23328.2(positive-feedback)-458.8(r)23.5(egulation)-470.6(of)-458.8(BMP)-470.6(signaling)-458.8(\()]TJ
1 1 0 0 k
51.0204 0 TD
[(W)35.3(ang)]TJ
-22.7851 -1.2118 TD
[(and)-329.4(Ferguson,)-317.6(2005)]TJ
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[(\).)-385.7(Ge-)]TJ
6.0742 -1.1857 TD
[(mental)-514.3(Pr)14.3(ocedur)14.3(es)-500(and)-514.3(can)-500(be)-514.3(found)-514.3(with)-500(this)-514.3(article)-500(online)-514.3(at)]TJ
-34.2857 -0.1 TD
[(notypes)-414.3(of)]TJ
/F5 1 Tf
5.4558 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 93.5036 362.0285 Tm
(/+)Tj
6.9636 0 0 6.9755 104.4173 359.5372 Tm
[(heter)14.3(ozygote)-414.3(female)-428.6(and)]TJ
/F5 1 Tf
12.1357 0 TD
(w/)Tj
/F3 1 Tf
1.5443 0 TD
(Dp\(1;Y\))Tj
/F5 1 Tf
3.371 0 TD
(y)Tj
5.173 0 0 4.5839 226.6349 362.0285 Tm
(+)Tj
6.9636 0 0 6.9755 232.7232 359.5372 Tm
(sog)Tj
5.173 0 0 4.5839 244.4637 362.0285 Tm
(+)Tj
6.9636 0 0 6.9755 250.4525 359.5372 Tm
(B)Tj
5.173 0 0 4.5839 255.3548 362.0285 Tm
(S)Tj
/F3 1 Tf
6.9636 0 0 6.9755 282.5232 351.2663 Tm
1 1 0 0 k
[(http://www)57.2(.developmentalcell.com/cgi/content/full/8/6/)]TJ
/F10 1 Tf
25.5995 0 TD
()Tj
/F3 1 Tf
2.283 0 TD
(/DC1/)Tj
0 0 0 1 k
2.704 0 TD
(.)Tj
-64.8722 -0.1 TD
[(male)-471.4(embryos)-485.7(r)14.3(esulting)-471.4(fr)14.3(om)-485.7(the)-471.4(cr)14.3(oss)-485.7(between)]TJ
/F5 1 Tf
23.6217 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 220.0038 353.06 Tm
(6)Tj
/F5 1 Tf
6.9636 0 0 6.9755 222.8801 350.5687 Tm
(/)Tj
/F3 1 Tf
0.8377 0 TD
(Dp\(1;Y\))Tj
/F5 1 Tf
3.371 0 TD
(y)Tj
5.173 0 0 4.5839 255.6693 353.06 Tm
(+)Tj
6.9636 0 0 6.9755 43.7712 341.6002 Tm
(sog)Tj
5.173 0 0 4.5839 55.5117 344.0915 Tm
(+)Tj
6.9636 0 0 6.9755 60.7047 341.6002 Tm
(B)Tj
5.173 0 0 4.5839 65.607 344.0915 Tm
0.3077 Tc
(Ss)Tj
/F3 1 Tf
6.9636 0 0 6.9755 75.1271 341.6002 Tm
0 Tc
[(males)-300(and)]TJ
/F5 1 Tf
5.0687 0 TD
(w)Tj
/F3 1 Tf
1.078 0 TD
[(females)-300(wer)14.3(e)-285.7(determined)-300(by)-285.7(the)-300(expr)14.3(ession)]TJ
-10.6495 -1.2857 TD
[(of)-314.3(the)-328.6(Sex)-314.3(lethal,)-328.6(a)-314.3(female-specific)-314.3(pr)14.3(otein.)-328.6(The)-314.3(same)-328.6(method)-314.3(was)]TJ
/F2 1 Tf
34.2857 -1.2571 TD
(Acknowledgments)Tj
/F3 1 Tf
-34.2857 -0.0286 TD
[(used)-442.8(to)-457.1(identify)-442.8(C\(1\)RM)]TJ
/F5 1 Tf
11.8029 0 TD
0.4429 Tc
(yw)Tj
/F3 1 Tf
1.7208 0 TD
0 Tc
(/Dp\(1:Y\))Tj
/F5 1 Tf
4.1658 0 TD
(y)Tj
5.173 0 0 4.5839 170.4356 326.1544 Tm
(+)Tj
6.9636 0 0 6.9755 176.7228 323.6632 Tm
(sog)Tj
5.173 0 0 4.5839 188.4633 326.1544 Tm
(+)Tj
6.9636 0 0 6.9755 194.6511 323.6632 Tm
(B)Tj
5.173 0 0 4.5839 199.5534 326.1544 Tm
(S)Tj
/F3 1 Tf
6.9636 0 0 6.9755 206.089 323.6632 Tm
[(female)-442.8(embryos)]TJ
-23.3095 -1.2857 TD
[(with)-614.3(extra)-628.6(copy)-614.3(of)]TJ
/F5 1 Tf
9.9183 0 TD
(sog)Tj
/F3 1 Tf
1.686 0 TD
[(,)-614.3(collected)-628.6(fr)14.3(om)-614.3(the)]TJ
/F5 1 Tf
10.571 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 209.9318 317.186 Tm
(6)Tj
6.9636 0 0 6.9755 212.8081 314.6947 Tm
(/C\(1\)RM,)Tj
/F5 1 Tf
4.6855 0 TD
0.6143 Tc
(yw)Tj
/F3 1 Tf
5.3258 -1.2571 TD
0 Tc
[(W)14.3(e)-457.1(thank)-457.1(D.)-471.4(Kosman)-457.1(for)-457.1(helpful)-457.1(assistance)-471.4(with)-457.1(confocal)-457.1(imag-)]TJ
/F5 1 Tf
-34.2857 -0.0286 TD
(f)Tj
/F3 1 Tf
0.315 0 TD
(/Dp\(1;Y\))Tj
/F5 1 Tf
3.7229 0 TD
(y)Tj
5.173 0 0 4.5839 75.3716 308.2175 Tm
(+)Tj
6.9636 0 0 6.9755 81.062 305.7262 Tm
(sog)Tj
5.173 0 0 4.5839 92.8024 308.2175 Tm
(+)Tj
6.9636 0 0 6.9755 98.3933 305.7262 Tm
(B)Tj
5.173 0 0 4.5839 103.2957 308.2175 Tm
(S)Tj
/F3 1 Tf
6.9636 0 0 6.9755 109.2344 305.7262 Tm
[(stock.)-357.1(T)114.3(o)-371.4(cr)14.3(eate)-357.1(lateralized)-371.4(embryos)-357.1(with)-371.4(st2-)]TJ
24.885 -1.2571 TD
[(ing)-500(and)-500(in)-485.7(situ)-500(hybridization)-500(and)-500(P)171.4(.)-500(ten)-500(Dijke)-485.7(and)-500(the)-500(Iowa)-500(Hy-)]TJ
/F5 1 Tf
-34.2857 -0.0286 TD
-0.0143 Tc
[(dp)14.3(p)]TJ
/F3 1 Tf
2.1473 0 TD
0 Tc
(\()Tj
1 1 0 0 k
0.2494 0 TD
-0.0143 Tc
[(Fig)14.3(ur)28.6(e)-357.1(3)]TJ
0 0 0 1 k
3.6792 0 TD
-0.0286 Tc
(\),)Tj
/F5 1 Tf
0.8846 0 TD
(gd)Tj
5.173 0 0 4.5839 100.3269 299.249 Tm
0 Tc
(7)Tj
6.9636 0 0 6.9755 105.6902 296.7577 Tm
-0.0143 Tc
[(so)14.3(g)]TJ
5.173 0 0 4.5839 117.0327 299.249 Tm
0 Tc
(U2)Tj
6.9636 0 0 6.9755 123.7423 296.7577 Tm
-0.0286 Tc
[(/g)-14.3(d)]TJ
5.173 0 0 4.5839 134.1796 299.249 Tm
0 Tc
(7)Tj
/F3 1 Tf
6.9636 0 0 6.9755 137.0559 296.7577 Tm
(;)Tj
/F5 1 Tf
0.6209 0 TD
-0.0143 Tc
[(mw)14.3(h[1)14.3(])-357.2(s)14.3(nk[)14.3(1])-357.2(red)14.3([1)14.3(])-357.2(e)0([)14.3(1)0(])-357.2(Tl[)14.3(3])-342.9(ca[)14.3(1])]TJ
/F3 1 Tf
15.9322 0 TD
(/+)Tj
4.3366 -1.2571 TD
0 Tc
[(bridoma)-385.7(Bank)-371.4(for)-385.7(antibodies.)-385.7(This)-371.4(work)-385.7(was)-385.7(supported)-371.4(by)-385.7(grants)]TJ
-34.2857 -0.0286 TD
[(females)-414.3(wer)14.3(e)-400(c)0(r)14.3(ossed)-414.3(to)]TJ
/F5 1 Tf
12.0869 0 TD
(yw)Tj
/F3 1 Tf
1.278 0 TD
[(;)-414.3(st2-)]TJ
/F5 1 Tf
2.4893 0 TD
(dpp)Tj
/F3 1 Tf
1.833 0 TD
(/st2-)Tj
/F5 1 Tf
2.149 0 TD
(dpp)Tj
/F3 1 Tf
2.233 0 TD
[(males.)-414.3(For)-400(scoring)]TJ
12.2167 -1.2571 TD
[(fr)14.3(om)-500(NIH)-500(\(R01NS29870)-500(to)-485.7(E.B.;)-500(P20GM66051)-500(and)-500(R01GM67247)]TJ
/F5 1 Tf
-34.2857 -0.0286 TD
(sog)Tj
5.173 0 0 4.5839 55.5117 281.312 Tm
()Tj
/F3 1 Tf
6.9636 0 0 6.9755 61.401 278.8207 Tm
[(embryos)-400(in)]TJ
1 1 0 0 k
5.6206 0 TD
[(Figur)14.3(es)-400(2E,)-400(2F)128.6(,)-400(and)-385.7(3B)]TJ
0 0 0 1 k
10.7627 0 TD
0.4 Tc
(,a)Tj
/F5 1 Tf
1.634 0 TD
0 Tc
(sog)Tj
/F3 1 Tf
2.086 0 TD
[(in)-400(situ)-385.7(pr)14.3(obe)-400(was)]TJ
11.6507 -1.2571 TD
[(to)-385.7(A.D.L.,)-400(F)128.6(.)0(Y)114.3(.M.W)71.4(.,)-385.7(Q.N.,)-385.7(and)-400(J.L.M.;)-385.7(RO1HD36081)-385.7(to)-400(J.L.M.;)-385.7(and)]TJ
-34.2857 -0.0286 TD
[(used)-300(in)-300(addition)-314.3(to)-300(discriminate)-300(embryos)-300(that)-314.3(lack)]TJ
/F5 1 Tf
23.5453 0 TD
(sog)Tj
/F3 1 Tf
1.986 0 TD
[(expr)14.3(ession.)]TJ
8.7545 -1.2571 TD
[(P01HD38761)-328.6(to)-328.6(A.D.L.\))-314.3(and)-328.6(the)-328.6(Human)-328.6(Fr)14.3(ontiers)-314.3(Science)-328.6(Pr)14.3(ogram)]TJ
-34.2857 -0.0286 TD
[(Embryo)-314.3(collections)-314.3(wer)14.3(e)-314.3(performed)-314.3(at)-314.3(25C.)]TJ
34.2857 -1.2571 TD
[(\(to)-314.3(A.D.L.\).)]TJ
-33.2857 -0.0286 TD
[(For)-542.9(the)-528.6(analysis)-542.9(of)]TJ
/F5 1 Tf
9.791 0 TD
(dpp)Tj
/F3 1 Tf
2.3758 0 TD
(and)Tj
/F5 1 Tf
2.2695 0 TD
(sog)Tj
/F3 1 Tf
2.2288 0 TD
[(gene)-542.9(dosage,)-542.9(we)-528.6(used)-542.8(the)]TJ
/F5 1 Tf
-17.6653 -1.2857 TD
(dpp)Tj
/F3 1 Tf
5.173 0 0 4.5839 56.5353 245.4379 Tm
(H46)Tj
/F5 1 Tf
6.9636 0 0 6.9755 69.2063 242.9467 Tm
(Sp)Tj
/F3 1 Tf
1.259 0 TD
[(/CyO23,)-457.1(Df\(2L\))-457.1(DTD48/CyO23,)-457.1(and)]TJ
/F5 1 Tf
16.9274 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 207.5891 245.4379 Tm
(6)Tj
6.9636 0 0 6.9755 210.4654 242.9467 Tm
(/Dp\(1;Y\))Tj
/F5 1 Tf
4.1801 0 TD
(y)Tj
/F3 1 Tf
0.5 0 TD
(+)Tj
/F5 1 Tf
1.0571 0 TD
(B)Tj
5.173 0 0 4.5839 255.3194 245.4379 Tm
(S)Tj
ET
q
0.999147 0 0 1.000854 0 0 cm
0 0 0 1 K
0 J 0 j 0.398 w 10 M []0 d
1 i
69.297 240.947 m
78.059 240.947 l
S
Q
BT
6.9636 0 0 6.9755 43.7712 233.9782 Tm
(sog)Tj
/F3 1 Tf
1.686 0 TD
[(+)-528.6(stocks.)]TJ
/F5 1 Tf
4.9921 0 TD
(dpp)Tj
/F3 1 Tf
5.173 0 0 4.5839 103.0387 236.4695 Tm
(/+)Tj
6.9636 0 0 6.9755 114.7482 233.9782 Tm
[(heter)14.3(ozygotes)-542.9(wer)14.3(e)-528.6(generated)-528.6(by)-528.6(cr)14.3(ossing)]TJ
24.0931 -0.5 TD
[(Received:)-314.3(September)-314.3(9,)-314.3(2004)]TJ
-34.2857 -0.7857 TD
[(Df\(2L\)DTD48/CyO23)-357.1(flies)-342.9(to)]TJ
/F5 1 Tf
13.192 0 TD
(w)Tj
/F3 1 Tf
0.778 0 TD
[(-)-342.8(and)-357.1(scoring)-342.8(the)-357.1(pr)14.3(ogeny)-342.8(for)-357.1(PMad)]TJ
20.3158 -0.5 TD
[(Revised:)-314.3(Mar)14.3(ch)-314.3(22,)-314.3(2005)]TJ
-34.2857 -0.7857 TD
[(staining,)-271.4(which)-271.4(fell)-257.1(into)-271.4(two)-271.4(clearly)-271.4(distinguishable)-257.1(classes:)-271.4(3)]TJ
/F5 1 Tf
28.7489 0 TD
(dpp)Tj
/F3 1 Tf
1.833 0 TD
(,)Tj
3.7038 -0.5 TD
[(Accepted:)-314.3(April)-314.3(20,)-314.3(2005)]TJ
-34.2857 -0.7857 TD
[(very)-342.9(str)14.3(ong)-342.8(staining;)-328.6(and)-342.8(1)]TJ
/F5 1 Tf
13.4015 0 TD
(dpp)Tj
/F3 1 Tf
1.833 0 TD
[(,)-342.9(weak)-328.6(staining.)-342.9(Double)-342.8(heter)14.3(ozy-)]TJ
19.0512 -0.5 TD
[(Published:)-314.3(June)-314.3(6,)-314.3(2005)]TJ
-34.2857 -0.7857 TD
(gous)Tj
/F5 1 Tf
2.6933 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 74.2664 200.5954 Tm
(/+)Tj
6.9636 0 0 6.9755 82.2952 198.1042 Tm
(;)Tj
/F5 1 Tf
0.678 0 TD
(dpp)Tj
/F3 1 Tf
5.173 0 0 4.5839 99.7806 200.5954 Tm
(/+)Tj
6.9636 0 0 6.9755 110.6943 198.1042 Tm
[(embryos)-414.3(wer)14.3(e)-414.3(generated)-400(by)-414.3(cr)14.3(ossing)]TJ
/F5 1 Tf
18.0543 0 TD
(dpp)Tj
/F3 1 Tf
5.173 0 0 4.5839 249.1816 200.5954 Tm
(H46)Tj
/F5 1 Tf
6.9636 0 0 6.9755 43.7712 189.1357 Tm
(Sp)Tj
/F3 1 Tf
1.259 0 TD
[(/CyO23)-285.7(females)-271.4(to)]TJ
/F5 1 Tf
8.8467 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 125.8839 191.6269 Tm
(6)Tj
6.9636 0 0 6.9755 128.7602 189.1357 Tm
(/Dp\(1;Y\))Tj
/F5 1 Tf
4.0087 0 TD
(y)Tj
/F3 1 Tf
5.173 0 0 4.5839 160.1567 191.6269 Tm
(+)Tj
/F5 1 Tf
6.9636 0 0 6.9755 165.1507 189.1357 Tm
(B)Tj
5.173 0 0 4.5839 170.053 191.6269 Tm
(S)Tj
6.9636 0 0 6.9755 175.3948 189.1357 Tm
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 187.1353 191.6269 Tm
(+)Tj
6.9636 0 0 6.9755 192.2288 189.1357 Tm
[(males)-271.4(and)-285.7(scr)14.3(eening)]TJ
/F2 1 Tf
12.9666 -0.5857 TD
(References)Tj
/F3 1 Tf
-34.2857 -0.7 TD
-0.0286 Tc
[(f)-14.3(e)0(m)-14.3(a)0(l)-14.3(e)-328.6(em)-14.3(br)-14.3(y)-14.3(o)0(s)-314.3(e)0(x)-14.3(p)-14.3(r)14.3(e)-14.3(s)0(s)-14.3(i)-14.3(n)0(g)-328.6(S)0(x)-14.3(l)-314.3(an)-14.3(d)-314.3(s)-14.3(c)-14.3(ored)-314.3(f)-14.3(o)0(r)-328.6(P)0(M)-14.3(a)-14.3(d)-300(s)-14.3(t)0(a)-14.3(i)-14.3(n)0(i)-14.3(n)0(g)-14.3(.)-328.6(Th)-14.3(es)-14.3(e)]TJ
0 -1.2857 TD
-0.0143 Tc
[(em)14.3(br)14.3(yos)-242.9(al)14.3(so)-242.9(f)14.3(e)0(l)14.3(l)-257.2(in)14.3(to)-228.6(two)-242.9(cl)14.3(ear)14.3(ly)-228.6(dis)14.3(ti)14.3(nct)-242.9(ca)14.3(teg)14.3(or)14.3(ies)14.3(:)]TJ
/F5 1 Tf
23.3315 0 TD
-0.0286 Tc
[(so)-14.3(g)]TJ
/F3 1 Tf
5.173 0 0 4.5839 217.5852 173.6899 Tm
0 Tc
(6)Tj
6.9636 0 0 6.9755 220.4615 171.1987 Tm
[(/)28.6(+)14.3(;)-228.6(+/CyO23)]TJ
8.9123 -0.6 TD
[(Alon,)-385.7(U.,)-385.7(Sur)14.3(ette,)-385.7(M.G.,)-385.7(Barkai,)-385.7(N.,)-400(and)-385.7(Leibler)85.7(,)-385.7(S)0(.)-385.7(\(1999\).)-385.7(Robust-)]TJ
-34.2857 -0.6857 TD
(\(1)Tj
/F5 1 Tf
1.8197 0 TD
(sog)Tj
/F3 1 Tf
1.686 0 TD
0.4 Tc
[(;3)400()]TJ
/F5 1 Tf
2.2197 0 TD
0 Tc
(dpp)Tj
/F3 1 Tf
2.233 0 TD
[(=)-385.7(very)-385.7(str)14.3(ong)-400(and)-385.7(br)14.3(oad)-400(PMad)-385.7(staining\))-400(and)-385.7(the)]TJ
26.3274 -0.6 TD
[(ness)-314.3(in)-314.3(bacterial)-314.3(chemotaxis.)-314.3(Natur)14.3(e)]TJ
/F5 1 Tf
17.2479 0 TD
(397)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(168171.)]TJ
-53.2016 -0.6857 TD
[(double)-271.4(heter)14.3(ozygotes,)]TJ
/F5 1 Tf
10.5694 0 TD
(sog)Tj
/F3 1 Tf
5.173 0 0 4.5839 129.1129 155.7529 Tm
(6)Tj
6.9636 0 0 6.9755 131.9892 153.2617 Tm
(/+;)Tj
/F5 1 Tf
1.5157 0 TD
(dpp)Tj
/F3 1 Tf
5.173 0 0 4.5839 155.3081 155.7529 Tm
(H46)Tj
6.9636 0 0 6.9755 164.7957 153.2617 Tm
[(/+)-271.4(\(1)]TJ
/F5 1 Tf
2.9288 0 TD
(sog)Tj
/F3 1 Tf
1.686 0 TD
0.2714 Tc
[(;1)271.4()]TJ
/F5 1 Tf
1.9911 0 TD
0 Tc
(dpp)Tj
/F3 1 Tf
2.1044 0 TD
[(=)-271.4(appr)14.3(oxi-)]TJ
8.1958 -0.9 TD
[(Ar)14.3(ora,)-285.7(K.,)-271.4(Levine,)-285.7(M.S.,)-285.7(and)-285.7(OConnor)85.7(,)-271.4(M.B.)-285.7(\(1994\).)-285.7(The)]TJ
/F5 1 Tf
25.5312 0 TD
(screw)Tj
/F3 1 Tf
3.0457 0 TD
(gene)Tj
-62.8626 -0.3857 TD
[(mately)-442.9(wild-type)-442.8(level)-457.1(of)-442.9(PMad)-442.9(staining)-442.9(with)-457.1(some)-442.9(irr)14.3(egularity)-442.8(in)]TJ
34.2857 -0.9 TD
[(encodes)-328.6(a)-314.3(ubiquitously)-328.6(expr)14.3(essed)-314.3(member)-328.6(of)-328.6(the)-314.3(TGF-beta)-328.6(family)]TJ
-34.2857 -0.3857 TD
[(patter)-14.3(n\).)]TJ
34.2857 -0.9 TD
[(r)14.3(equir)14.3(ed)-542.9(for)-557.1(specification)-542.9(of)-557.1(dorsal)-542.9(cell)-557.1(fates)-542.8(in)-542.8(the)]TJ
/F5 1 Tf
25.85 0 TD
(Drosophila)Tj
/F3 1 Tf
-25.85 -1.2857 TD
[(embryo.)-314.3(Genes)-314.3(Dev)71.4(.)]TJ
/F5 1 Tf
9.6893 0 TD
(8)Tj
/F3 1 Tf
0.556 0 TD
[(,)-314.3(25882601.)]TJ
/F2 1 Tf
-44.531 -0.9286 TD
[(Immunofluorescence)-314.3(and)-314.3(In)-314.3(Situ)-314.3(Hybridization)]TJ
/F3 1 Tf
34.2857 -0.6571 TD
[(Ashe,)-371.4(H.L.)-357.1(\(2002\).)-371.4(BMP)-357.1(signalling:)-371.4(visualisation)-357.1(of)-371.4(the)-357.1(Sog)-371.4(pr)14.3(otein)]TJ
-34.2857 -0.6286 TD
[(A)-271.4(detailed)-257.1(description)-271.4(of)-271.4(fluor)14.3(escent)-257.1(methods)-271.4(used)-271.4(to)-257.1(detect)-271.4(multi-)]TJ
34.2857 -0.6571 TD
[(gradient.)-314.3(Curr)85.7(.)-314.3(Biol.)]TJ
/F5 1 Tf
9.286 0 TD
(12)Tj
/F3 1 Tf
1.112 0 TD
[(,)-314.3(R273R275.)]TJ
-44.6837 -0.6286 TD
[(ple)-371.4(RNA)-357.1(transcripts)-371.4(is)-371.4(given)-357.1(in)]TJ
1 1 0 0 k
14.7048 0 TD
[(Kosman)-357.1(et)-371.4(al.)-371.4(\(2004\))]TJ
0 0 0 1 k
9.6409 0 TD
[(.)-357.1(P)0(r)14.3(obes)-371.4(wer)14.3(e)]TJ
9.94 -0.9714 TD
[(Ashe,)-371.4(H.L.,)-371.4(and)-371.4(Levine,)-371.4(M.)-385.7(\(1999\).)-371.4(Local)-371.4(inhibition)-371.4(and)-371.4(long-range)]TJ
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[(labeled)-442.8(with)-442.8(digoxigenin,)-442.9(biotin,)-457.1(fluor)14.3(escein)-442.9(\(Roche\),)-442.9(and)-442.8(dinitr)14.3(o-)]TJ
34.2857 -0.9714 TD
[(enhancement)-614.3(of)-614.3(Dpp)-614.3(signal)-614.3(transduction)-628.6(by)-614.3(Sog.)-614.3(Natur)14.3(e)]TJ
/F5 1 Tf
28.9199 0 TD
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(,)Tj
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[(phenol)-500(\(NEN\))-514.3(haptens.)-500(For)-514.3(double)-500(pr)14.3(otein)-514.3(detection)-500(and)-514.3(in)-500(situ)]TJ
34.2857 -0.9714 TD
(427431.)Tj
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[(staining,)-242.9(fixed)-242.8(embryos)-242.8(wer)14.3(e)-242.8(t)0(r)14.3(eated)-242.8(with)-242.9(acetone)-242.8(\(10)-242.8(min)-242.9(at)-242.9(20C\))]TJ
0 -1.2857 TD
[(befor)14.3(e)-300(hybridization)-300(to)-300(allow)-300(penetration)-300(of)-300(pr)14.3(obes,)-300(as)-300(a)-300(substitute)-3419.7(Ashe,)-471.4(H.L.,)-471.4(Mannervik,)-485.7(M.,)-471.4(and)-471.4(Levine,)-471.4(M.)-485.7(\(2000\).)-471.4(Dpp)-471.4(signaling)]TJ
34.2857 -1.2857 TD
[(thr)14.3(esholds)-257.1(in)-257.1(the)-242.8(dorsal)-257.1(ectoderm)-257.1(of)-257.1(the)]TJ
/F5 1 Tf
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(Drosophila)Tj
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5.2581 0 TD
[(embryo.)-257.1(Devel-)]TJ
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[(for)-400(pr)14.3(oteinase)-385.7(K)-400(incubation)-400(\()]TJ
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13.5383 0 TD
[(Nagaso)-385.7(et)-400(al.,)-400(2001)]TJ
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[(\).)-400(After)-385.7(this)-400(tr)14.3(eat-)]TJ
-22.7289 -1.2857 TD
[(ment,)-400(in)-414.3(situ)-400(hybridization)-400(was)-400(performed)-414.3(befor)14.3(e)-400(immunostaining)-3427.8(opment)]TJ
/F5 1 Tf
38.137 0 TD
(127)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(33053312.)]TJ
ET
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BT
/F3 1 Tf
6.9636 0 0 6.9755 86.5476 750.3645 Tm
0 0 0 1 k
0 Tc
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[(Origin)-314.3(of)-314.3(a)-314.3(BMP)-314.3(Activity)-314.3(Gradient)]TJ
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[(Balemans,)-428.6(W)71.4(.)0(,)-442.9(and)-428.6(V)57.2(a)0(n)-428.6(Hul,)-442.9(W)71.4(.)-428.6(\(2002\).)-428.6(Extracellular)-442.8(r)14.3(egulation)-428.6(of)-3423.4(Lindsley)85.7(,)-371.4(D.L.,)-385.7(and)-371.4(Zimm,)-385.7(G.G.)-371.4(\(1992\).)-385.7(The)-371.4(Genome)-385.7(of)]TJ
/F5 1 Tf
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(Drosophila)Tj
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(melanogaster)Tj
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[(,)-314.3(First)-314.3(edition)-314.3(\(San)-314.3(Diego:)-314.3(Academic)-314.3(Pr)14.3(ess\).)]TJ
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/F5 1 Tf
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[(,)-314.3(231250.)]TJ
32.6177 -0.3 TD
[(Maduzia,)-328.6(L.L.,)-342.9(and)-328.6(Padgett,)-342.9(R.W)71.4(.)-328.6(\(1997\).)]TJ
/F5 1 Tf
19.0596 0 TD
(Drosophila)Tj
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5.3295 0 TD
[(MAD,)-342.9(a)-328.6(mem-)]TJ
-24.3891 -1.2857 TD
[(ber)-357.1(of)-371.4(the)-357.1(Smad)-357.1(family)85.7(,)-371.4(translocates)-357.1(to)-357.1(the)-357.1(nucleus)-371.4(upon)-357.1(stimula-)]TJ
-34.2857 -0.0429 TD
[(Biehs,)-457.1(B.,)-457.1(Francois,)-457.1(V)128.6(.)0(,)-457.1(and)-457.1(Bier)85.7(,)-471.4(E)0(.)-457.1(\(1996\).)-457.1(The)]TJ
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23.036 0 TD
[(Drosophila)-457.1(short)]TJ
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11.2497 -1.2429 TD
[(tion)-428.6(of)-442.9(the)-428.6(dpp)-442.8(pathway)85.7(.)-428.6(Biochem.)-442.9(Biophys.)-428.6(Res.)-442.8(Commun.)]TJ
/F5 1 Tf
28.9272 0 TD
(238)Tj
/F3 1 Tf
1.668 0 TD
(,)Tj
/F5 1 Tf
-64.8809 -0.0429 TD
(gastrulation)Tj
/F3 1 Tf
5.7639 0 TD
[(gene)-300(pr)14.3(events)-300(Dpp)-314.3(fr)14.3(om)-300(autoactivating)-300(and)-300(suppr)14.3(ess-)]TJ
28.5218 -1.2429 TD
(595598.)Tj
-34.2857 -0.0429 TD
[(ing)-257.1(neur)14.3(ogenesis)-257.1(in)-257.1(the)-271.4(neur)14.3(oectoderm.)-257.1(Genes)-257.1(Dev)71.4(.)]TJ
/F5 1 Tf
24 0 TD
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1.112 0 TD
[(,)-257.1(29222934.)]TJ
9.1738 -1.5429 TD
[(Markstein,)-285.7(M.,)-300(Markstein,)-285.7(P)171.4(.)0(,)-300(Markstein,)-285.7(V)128.6(.)0(,)-300(and)-285.7(Levine,)-300(M.S.)-285.7(\(2002\).)]TJ
-34.2857 -0.0857 TD
[(Campos-Ortega,)-471.4(J.A.,)-471.4(and)-471.4(Hartenstein,)-485.7(V)128.6(.)-471.4(\(1985\).)-471.4(The)-471.4(Embryonic)]TJ
34.2857 -1.2 TD
[(Genome-wide)-385.7(analysis)-371.4(of)-385.7(cluster)14.3(ed)-385.7(Dorsal)-385.7(binding)-371.4(sites)-385.7(identifies)]TJ
-34.2857 -0.0857 TD
[(Development)-642.9(of)]TJ
/F5 1 Tf
8.3103 0 TD
[(Drosophila)-642.9(melanogaster)]TJ
/F3 1 Tf
11.875 0 TD
[(,)-642.9(First)-628.6(Edition)-642.8(\(Berlin:)]TJ
14.1004 -1.2 TD
[(putative)-371.4(target)-371.4(genes)-371.4(in)-371.4(the)]TJ
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13.3647 0 TD
(Drosophila)Tj
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5.3724 0 TD
[(embryo.)-371.4(Pr)14.3(oc.)-371.4(Natl.)-371.4(Acad.)]TJ
-53.0228 -0.0857 TD
[(Springer)-314.3(V)57.2(erlag\).)]TJ
34.2857 -1.2 TD
[(Sci.)-314.3(USA)]TJ
/F5 1 Tf
4.3885 0 TD
(99)Tj
/F3 1 Tf
1.112 0 TD
[(,)-314.3(763768.)]TJ
-39.7862 -0.4286 TD
[(Chang,)-457.1(C.,)-457.1(Holtzman,)-471.4(D.A.,)-457.1(Chau,)-457.1(S.,)-457.1(Chickering,)-471.4(T)114.3(.)0(,)-457.1(W)14.3(oolf,)-457.1(E.A.,)]TJ
34.2857 -1.1571 TD
[(Mar)14.3(ques,)-257.1(G.,)-257.1(Musacchio,)-242.9(M.,)-257.1(Shimell,)-257.1(M.J.,)-257.1(W)14.3(unnenberg-Stapleton,)]TJ
-34.2857 -0.1286 TD
[(Holmgr)14.3(en,)-271.4(L.M.,)-271.4(Bodor)14.3(ova,)-271.4(J.,)-271.4(Gearing,)-257.1(D.P)171.4(.,)-271.4(Holmes,)-271.4(W)71.4(.E.,)-271.4(and)-271.4(Bri-)]TJ
34.2857 -1.1571 TD
[(K.,)-300(Cho,)-314.3(K.W)71.4(.,)-300(and)-314.3(OConnor)85.7(,)-300(M.B.)-314.3(\(1997\).)-300(Pr)14.3(oduction)-314.3(of)-300(a)-314.3(DPP)-300(ac-)]TJ
-34.2857 -0.1286 TD
[(vanlou,)-471.4(A.H.)-457.1(\(2001\).)-471.4(T)114.3(wisted)-457.1(gastrulation)-471.4(can)-457.1(function)-471.4(as)-457.1(a)-471.4(BMP)]TJ
34.2857 -1.1571 TD
[(tivity)-271.4(gradient)-285.7(in)-271.4(the)-271.4(early)]TJ
/F5 1 Tf
11.8896 0 TD
(Drosophila)Tj
/F3 1 Tf
5.2724 0 TD
[(embryo)-271.4(thr)14.3(ough)-285.7(the)-271.4(opposing)]TJ
-51.4476 -0.1286 TD
[(antagonist.)-314.3(Natur)14.3(e)]TJ
/F5 1 Tf
8.8572 0 TD
(410)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(483487.)]TJ
23.7606 -1.1571 TD
[(actions)-314.3(of)-314.3(the)-314.3(SOG)-314.3(and)-314.3(TLD)-314.3(pr)14.3(oteins.)-314.3(Cell)]TJ
/F5 1 Tf
19.8568 0 TD
(91)Tj
/F3 1 Tf
1.112 0 TD
[(,)-314.3(417426.)]TJ
-55.2545 -0.4714 TD
[(Decotto,)-471.4(E.,)-471.4(and)-485.7(Ferguson,)-471.4(E.L.)-471.4(\(2001\).)-471.4(A)-471.4(positive)-485.7(r)14.3(ole)-471.4(for)-471.4(Short)]TJ
34.2857 -1.1143 TD
[(Mason,)-500(E.D.,)-500(Konrad,)-485.7(K.D.,)-500(W)14.3(ebb,)-500(C.D.,)-500(and)-485.7(Marsh,)-500(J.L.)-500(\(1994\).)]TJ
-34.2857 -0.1714 TD
[(gastrulation)-714.3(in)-700(modulating)-714.3(BMP)-714.3(signaling)-700(during)-714.3(dorsoventral)]TJ
34.2857 -1.1143 TD
[(Dorsal)-314.3(midline)-328.6(fate)-314.3(in)]TJ
/F5 1 Tf
10.1633 0 TD
(Drosophila)Tj
/F3 1 Tf
5.3152 0 TD
[(embryos)-328.6(r)14.3(equir)14.3(es)]TJ
/F5 1 Tf
8.3952 0 TD
[(twisted)-314.3(gastru-)]TJ
/F3 1 Tf
-58.1594 -0.1714 TD
[(patter)-14.3(ning)-257.1(in)-242.8(the)]TJ
/F5 1 Tf
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(Drosophila)Tj
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5.2438 0 TD
[(embryo.)-257.1(Development)]TJ
/F5 1 Tf
10.4099 0 TD
(128)Tj
/F3 1 Tf
1.668 0 TD
[(,)-257.1(38313841.)]TJ
/F5 1 Tf
9.1918 -1.1143 TD
(lation)Tj
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2.538 0 TD
[(,)-371.4(a)-371.4(gene)-371.4(encoding)-371.4(a)-371.4(secr)14.3(eted)-371.4(pr)14.3(otein)-371.4(r)14.3(elated)-371.4(to)-371.4(human)-371.4(con-)]TJ
-36.8237 -0.5143 TD
[(Dorfman,)-300(R.,)-285.7(and)-300(Shilo,)-285.7(B.Z.)-300(\(2001\).)-300(Biphasic)-285.7(activation)-300(of)-285.7(the)-300(BMP)]TJ
34.2857 -0.7714 TD
[(nective)-314.3(tissue)-314.3(gr)14.3(owth)-314.3(factor)85.7(.)-314.3(Genes)-314.3(Dev)71.4(.)]TJ
/F5 1 Tf
19.0361 0 TD
(8)Tj
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0.556 0 TD
[(,)-314.3(14891501.)]TJ
-53.8778 -0.5143 TD
[(pathway)-385.7(patter)-14.3(ns)-385.7(the)]TJ
/F5 1 Tf
10.3953 0 TD
(Drosophila)Tj
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5.4009 0 TD
[(embryonic)-385.7(dorsal)-385.7(r)14.3(egion.)-385.7(Devel-)]TJ
18.4895 -1.0714 TD
[(Mason,)-657.1(E.D.,)-642.9(Williams,)-657.1(S.,)-657.1(Gr)14.3(otendorst,)-642.8(G.R.,)-657.1(and)-642.9(Marsh,)-657.1(J.L.)]TJ
-34.2857 -0.2143 TD
(opment)Tj
/F5 1 Tf
3.8512 0 TD
(128)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(965972.)]TJ
28.7665 -1.0714 TD
[(\(1997\).)-342.9(Combinatorial)-342.8(signaling)-342.8(by)-328.6(T)114.3(wisted)-342.8(Gastrulation)-342.9(and)-342.8(Deca-)]TJ
-34.2857 -0.5571 TD
[(Dubois,)-271.4(L.,)-271.4(Lecourtois,)-257.1(M.,)-271.4(Alexandr)14.3(e,)-271.4(C.,)-271.4(Hirst,)-271.4(E.,)-257.1(and)-271.4(V)-14.3(incent,)-271.4(J.P)171.4(.)]TJ
34.2857 -0.7286 TD
[(pentaplegic.)-314.3(Mech.)-314.3(Dev)71.4(.)]TJ
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11.5053 0 TD
(64)Tj
/F3 1 Tf
1.112 0 TD
[(,)-314.3(6175.)]TJ
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[(\(2001\).)-385.7(Regulated)-371.4(endocytic)-385.7(r)14.3(outing)-385.7(modulates)-371.4(wingless)-385.7(signaling)]TJ
34.2857 -1.0286 TD
[(Meinhar)14.3(dt,)-400(H.,)-400(and)-400(Roth,)-400(S.)-414.3(\(2002\).)-400(Developmental)-400(biology:)-400(sharp)]TJ
-34.2857 -0.2571 TD
(in)Tj
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(Drosophila)Tj
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5.3152 0 TD
[(embryos.)-314.3(Cell)]TJ
/F5 1 Tf
6.6865 0 TD
(105)Tj
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1.668 0 TD
[(,)-314.3(613624.)]TJ
19.4868 -1.0286 TD
[(peaks)-314.3(fr)14.3(om)-314.3(shallow)-314.3(sour)14.3(ces.)-314.3(Natur)14.3(e)]TJ
/F5 1 Tf
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(419)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(261262.)]TJ
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[(Eldar)85.7(,)-328.6(A.,)-328.6(Dorfman,)-342.9(R.,)-328.6(W)14.3(eiss,)-328.6(D.,)-328.6(Ashe,)-328.6(H.,)-328.6(Shilo,)-342.8(B.Z.,)-328.6(and)-328.6(Barkai,)]TJ
34.2857 -0.9857 TD
[(Mor)14.3(ohashi,)-285.7(M.,)-300(Winn,)-285.7(A.E.,)-300(Borisuk,)-285.7(M.T)114.3(.,)-300(Bolouri,)-285.7(H.,)-300(Doyle,)-285.7(J.,)-300(and)]TJ
-34.2857 -0.3 TD
[(N.)-257.1(\(2002\).)-257.1(Robustness)-271.4(of)-257.1(the)-257.1(BMP)-257.1(morphogen)-271.4(gradient)-257.1(in)]TJ
/F5 1 Tf
26.4805 0 TD
(Drosoph-)Tj
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7.8052 -0.9857 TD
[(Kitano,)-328.6(H.)-328.6(\(2002\).)-342.8(Robustness)-328.6(as)-328.6(a)-328.6(measur)14.3(e)-328.6(o)0(f)-342.8(plausibility)-328.6(in)-328.6(mod-)]TJ
/F5 1 Tf
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(ila)Tj
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1.3523 0 TD
[(embryonic)-314.3(patter)-14.3(ning.)-314.3(Natur)14.3(e)]TJ
/F5 1 Tf
13.9087 0 TD
(419)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(304308.)]TJ
17.3568 -0.9857 TD
[(els)-314.3(of)-314.3(biochemical)-314.3(networks.)-314.3(J.)-314.3(Theor)85.7(.)-314.3(Biol.)]TJ
/F5 1 Tf
6.9636 0 0 6.9755 466.459 454.7031 Tm
(216)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(1930.)]TJ
-56.2247 -0.6429 TD
[(Eldar)85.7(,)-700(A.,)-685.7(Rosin,)-700(D.,)-700(Shilo,)-700(B.Z.,)-685.7(and)-700(Barkai,)-700(N.)-685.7(\(2003\).)-700(Self-)]TJ
34.2857 -0.9429 TD
[(Nagaso,)-314.3(H.,)-328.6(Murata,)-314.3(T)114.3(.)0(,)-314.3(Day)85.7(,)-328.6(N.,)-314.3(and)-314.3(Y)85.7(okoyama,)-314.3(K.K.)-328.6(\(2001\).)-314.3(Simul-)]TJ
-34.2857 -0.3429 TD
[(enhanced)-385.7(ligand)-385.7(degradation)-385.7(underlies)-400(r)14.3(obustness)-385.7(of)-385.7(morphogen)]TJ
34.2857 -0.9429 TD
[(taneous)-357.1(detection)-342.8(of)-357.1(RNA)-342.8(and)-357.1(pr)14.3(otein)-357.1(by)-342.8(in)-357.1(situ)-342.8(hybridization)-357.1(and)]TJ
-34.2857 -0.3429 TD
[(gradients.)-314.3(Dev)71.4(.)-314.3(Cell)]TJ
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9.3193 0 TD
(5)Tj
/F3 1 Tf
0.556 0 TD
[(,)-314.3(635646.)]TJ
24.4104 -0.9429 TD
[(immunological)-314.3(staining.)-314.3(J.)-314.3(Histochem.)-314.3(Cytochem.)]TJ
/F5 1 Tf
23.2811 0 TD
(49)Tj
/F3 1 Tf
1.112 0 TD
[(,)-314.3(11771182.)]TJ
-58.6788 -0.6857 TD
[(Ferguson,)-314.3(E.L.,)-328.6(and)-314.3(Anderson,)-314.3(K.V)128.6(.)-314.3(\(1992\).)-328.6(Localized)-314.3(enhancement)]TJ
34.2857 -0.9 TD
[(Nguyen,)-300(M.,)-285.7(Park,)-300(S.,)-300(Mar)14.3(ques,)-285.7(G.,)-300(and)-300(Ar)14.3(ora,)-300(K.)-285.7(\(1998\).)-300(Interpr)14.3(eta-)]TJ
-34.2857 -0.3857 TD
[(and)-242.8(r)14.3(epr)14.3(ession)-242.8(of)-242.9(the)-242.8(activity)-242.8(of)-242.9(the)-242.9(TGF-beta)-242.8(family)-242.8(member)85.7(,)-242.9(deca-)]TJ
34.2857 -0.9 TD
[(tion)-328.6(of)-314.3(a)-328.6(BMP)-328.6(activity)-328.6(gradient)-314.3(in)]TJ
/F5 1 Tf
15.6652 0 TD
(Drosophila)Tj
/F3 1 Tf
5.3295 0 TD
[(embryos)-314.3(depends)-328.6(on)]TJ
-55.2804 -0.3857 TD
[(pentaplegic,)-257.1(is)-242.9(necessary)-257.1(for)-242.8(dorsal-ventral)-257.1(patter)-14.3(n)-257.1(formation)-242.9(in)-257.1(the)]TJ
34.2857 -0.9 TD
[(synergistic)-271.4(signaling)-271.4(by)-285.7(two)-271.4(type)-271.4(I)-271.4(r)14.3(eceptors,)-271.4(SAX)-271.4(and)-285.7(TKV)128.6(.)-271.4(Cell)]TJ
/F5 1 Tf
29.4741 0 TD
(95)Tj
/F3 1 Tf
1.112 0 TD
(,)Tj
/F5 1 Tf
-64.8718 -0.3857 TD
(Drosophila)Tj
/F3 1 Tf
5.3152 0 TD
[(embryo.)-314.3(Development)]TJ
/F5 1 Tf
10.5384 0 TD
(114)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(583597.)]TJ
16.7641 -0.9 TD
(495506.)Tj
-34.2857 -0.7286 TD
[(Francois,)-528.6(V)128.6(.)0(,)-528.6(Solloway)85.7(,)-528.6(M.,)-528.6(ONeill,)-528.6(J.W)71.4(.,)-528.6(Emery)85.7(,)-528.6(J.,)-528.6(and)-528.6(Bier)85.7(,)-528.6(E)0(.)]TJ
34.2857 -0.8571 TD
[(Raftery)85.7(,)-442.9(L.A.,)-428.6(and)-442.9(Sutherland,)-428.6(D.J.)-442.9(\(1999\).)-428.6(TGF-beta)-442.8(family)-428.6(signal)]TJ
-34.2857 -0.4286 TD
[(\(1994\).)-585.7(Dorsal-ventral)-600(patter)-14.3(ning)-585.7(of)-585.7(the)]TJ
/F5 1 Tf
19.6119 0 TD
(Drosophila)Tj
/F3 1 Tf
5.6009 0 TD
[(embryo)-585.7(de-)]TJ
9.0729 -0.8571 TD
[(transduction)-300(in)]TJ
/F5 1 Tf
7.2166 0 TD
(Drosophila)Tj
/F3 1 Tf
5.3009 0 TD
[(development:)-300(fr)14.3(om)-285.7(Mad)-300(to)-285.7(Smads.)-300(Dev)71.4(.)]TJ
-46.8033 -0.4286 TD
[(pends)-371.4(on)-371.4(a)-357.1(putative)-371.4(negative)-371.4(gr)14.3(owth)-371.4(factor)-371.4(encoded)-357.1(by)-371.4(the)]TJ
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(short)Tj
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5.7916 -0.8571 TD
(Biol.)Tj
/F5 1 Tf
2.3713 0 TD
(210)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(251268.)]TJ
/F5 1 Tf
-38.325 -0.4286 TD
(gastrulation)Tj
/F3 1 Tf
5.7782 0 TD
[(gene.)-314.3(Genes)-314.3(Dev)71.4(.)]TJ
/F5 1 Tf
8.4673 0 TD
(8)Tj
/F3 1 Tf
0.556 0 TD
[(,)-314.3(26022616.)]TJ
19.4842 -1.1571 TD
[(Ray)85.7(,)-400(R.P)171.4(.,)-400(and)-414.3(Wharton,)-400(K.A.)-400(\(2001\).)-400(T)114.3(wisted)-414.3(perspective:)-400(new)-400(in-)]TJ
-34.2857 -0.4714 TD
[(Harland,)-285.7(R.M.)-300(\(2001\).)-285.7(Developmental)-300(biology)85.7(.)-285.7(A)-300(twist)-285.7(on)-300(embryonic)]TJ
34.2857 -0.8143 TD
[(sights)-300(into)-300(extracellular)-300(modulation)-300(of)-285.7(BMP)-300(signaling)-300(during)-300(devel-)]TJ
-34.2857 -0.4714 TD
[(signalling.)-314.3(Natur)14.3(e)]TJ
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[(,)-314.3(423424.)]TJ
24.2596 -0.8143 TD
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[(,)-314.3(801804.)]TJ
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34.2857 -0.7714 TD
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[(dorsalizing)-457.1(factor)-457.1(noggin)-442.9(ventralizes)]TJ
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(Drosophila)Tj
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[(embryos)-457.1(by)]TJ
/F5 1 Tf
9.0305 -0.7714 TD
(sophila)Tj
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[(embryo.)-314.3(Development)]TJ
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[(,)-314.3(3554.)]TJ
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[(,)-314.3(607617.)]TJ
10.4656 -1.0714 TD
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[(Houchmandzadeh,)-285.7(B.,)-300(Wieschaus,)-285.7(E.,)-285.7(and)-285.7(Leibler)85.7(,)-300(S)0(.)-285.7(\(2002\).)-285.7(Estab-)]TJ
34.2857 -0.7286 TD
[(Hermanson,)-257.1(S.,)-271.4(Ekker)85.7(,)-257.1(S.C.,)-257.1(OConnor)85.7(,)-271.4(M.B.,)-257.1(and)-257.1(Marsh,)-271.4(J.L.)-257.1(\(2001\).)]TJ
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[(lishment)-428.6(of)-428.6(developmental)-414.3(pr)14.3(ecision)-428.6(and)-428.6(pr)14.3(oportions)-428.6(in)-414.3(the)-428.6(early)]TJ
34.2857 -0.7286 TD
[(T)114.3(wisted)-385.7(gastrulation)-371.4(is)-385.7(a)-371.4(conserved)-385.7(extracellular)-371.4(BMP)-385.7(antagonist.)]TJ
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(Drosophila)Tj
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[(,)-314.3(798802.)]TJ
19.8163 -0.7286 TD
[(Natur)14.3(e)]TJ
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[(,)-314.3(479483.)]TJ
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34.2857 -0.6857 TD
[(Rusch,)-271.4(J.,)-257.1(and)-271.4(Levine,)-257.1(M.)-271.4(\(1996\).)-271.4(Thr)14.3(eshold)-257.1(r)14.3(esponses)-271.4(to)-257.1(the)-271.4(dorsal)]TJ
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[(r)14.3(equir)14.3(ed)-500(for)-500(dorsal-ventral)-500(patter)-14.3(ning)-500(of)-500(the)]TJ
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(Drosophila)Tj
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(embryo.)Tj
7.2003 -0.6857 TD
[(r)14.3(egulatory)-300(gradient)-285.7(and)-300(the)-300(subdivision)-285.7(of)-300(primary)-285.7(tissue)-300(territories)]TJ
-34.2857 -0.6 TD
[(Genes)-314.3(Dev)71.4(.)]TJ
/F5 1 Tf
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[(,)-314.3(868879.)]TJ
28.1337 -0.6857 TD
[(in)-314.3(the)]TJ
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(Drosophila)Tj
/F3 1 Tf
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[(embryo.)-314.3(Curr)85.7(.)-314.3(Opin.)-314.3(Genet.)-314.3(Dev)71.4(.)]TJ
/F5 1 Tf
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[(,)-314.3(416423.)]TJ
-58.1296 -0.9429 TD
[(Jazwinska,)-300(A.,)-300(Rushlow)57.2(,)-300(C.,)-300(and)-300(Roth,)-285.7(S.)-300(\(1999\).)-300(The)-300(r)14.3(ole)-300(of)-300(brinker)]TJ
34.2857 -0.6429 TD
[(Rusch,)-371.4(J.,)-357.1(and)-371.4(Levine,)-371.4(M.)-357.1(\(1997\).)-371.4(Regulation)-357.1(of)-371.4(a)-371.4(dpp)-357.1(target)-371.4(gene)]TJ
-34.2857 -0.6429 TD
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(Drosophila)Tj
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(em-)Tj
6.9636 0 0 6.9755 325.2996 213.7494 Tm
[(in)-314.3(the)]TJ
/F5 1 Tf
2.9065 0 TD
(Drosophila)Tj
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[(embryo.)-314.3(Development)]TJ
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[(bryos.)-314.3(Development)]TJ
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[(,)-314.3(33233334.)]TJ
22.9863 -0.9429 TD
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[(Jortikka,)-385.7(L.,)-385.7(Laitinen,)-371.4(M.,)-385.7(Lindholm,)-385.7(T)114.3(.S.,)-385.7(and)-371.4(Marttinen,)-385.7(A.)-385.7(\(1997\).)]TJ
34.2857 -0.5857 TD
[(T)85.7(ranscriptional)-257.1(r)14.3(egulation)-271.4(of)-257.1(the)]TJ
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(Drosophila)Tj
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[(gene)-271.4(zen)-257.1(by)-271.4(competing)]TJ
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[(Inter)-14.3(nalization)-314.3(and)-314.3(intracellular)-314.3(pr)14.3(ocessing)-314.3(of)-314.3(bone)-314.3(morphogenetic)]TJ
34.2857 -0.5857 TD
[(Smad)-314.3(and)-314.3(Brinker)-314.3(inputs.)-314.3(Genes)-314.3(Dev)71.4(.)]TJ
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[(,)-314.3(340351.)]TJ
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[(pr)14.3(otein)-314.3(\(BMP\))-314.3(in)-328.6(rat)-314.3(skeletal)-314.3(muscle)-314.3(myoblasts)-314.3(\(L6\).)-328.6(Cell.)-314.3(Signal.)]TJ
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3.692 -0.8857 TD
[(Scott,)-414.3(I.C.,)-428.6(Blitz,)-414.3(I.L.,)-414.3(Pappano,)-428.6(W)71.4(.N.,)-414.3(Maas,)-414.3(S.A.,)-414.3(Cho,)-428.6(K.W)71.4(.,)-414.3(and)]TJ
-34.2857 -0.4 TD
(4751.)Tj
34.2857 -0.8857 TD
[(Gr)14.3(eenspan,)-485.7(D.S.)-471.4(\(2001\).)-485.7(Homologues)-471.4(of)-485.7(T)114.3(wisted)-471.4(gastrulation)-485.7(ar)14.3(e)]TJ
-34.2857 -0.7571 TD
[(Kawano,)-314.3(Y)114.3(.)0(,)-328.6(and)-314.3(Kypta,)-328.6(R.)-314.3(\(2003\).)-328.6(Secr)14.3(eted)-314.3(antagonists)-328.6(of)-314.3(the)-328.6(Wnt)]TJ
34.2857 -0.5286 TD
[(extracellular)-528.6(cofactors)-528.6(in)-528.6(antagonism)-542.8(of)-528.6(BMP)-528.6(signalling.)-528.6(Natur)14.3(e)]TJ
-34.2857 -0.7571 TD
[(signalling)-314.3(pathway)85.7(.)-314.3(J)0(.)-314.3(Cell)-314.3(Sci.)]TJ
/F5 1 Tf
14.3615 0 TD
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1.668 0 TD
[(,)-314.3(26272634.)]TJ
/F5 1 Tf
18.2562 -0.5286 TD
(410)Tj
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[(,)-314.3(475478.)]TJ
-35.9537 -1.1143 TD
[(Kosman,)-328.6(D.,)-328.6(Mizutani,)-342.9(C.M.,)-328.6(Lemons,)-328.6(D.,)-328.6(Cox,)-342.8(W)71.4(.G.,)-328.6(McGinnis,)-328.6(W)71.4(.)0(,)]TJ
34.2857 -0.4714 TD
[(Shimell,)-542.9(M.J.,)-557.1(Ferguson,)-542.9(E.L.,)-542.9(Childs,)-557.1(S.R.,)-542.9(and)-557.1(OConnor)85.7(,)-542.8(M.B.)]TJ
-34.2857 -0.8143 TD
[(and)-357.1(Bier)85.7(,)-357.1(E)0(.)-357.1(\(2004\).)-357.1(Multiplex)-357.1(detection)-371.4(of)-357.1(RNA)-357.1(expr)14.3(ession)-357.1(in)]TJ
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(Dro-)Tj
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5.5124 -0.4714 TD
[(\(1991\).)-342.9(The)]TJ
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(Drosophila)Tj
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[(dorsal-ventral)-342.9(patter)-14.3(ning)-342.8(gene)-357.1(tolloid)-342.8(is)-342.9(r)14.3(e)0(-)]TJ
/F5 1 Tf
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(sophila)Tj
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[(embryos.)-314.3(Science)]TJ
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(305)Tj
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[(,)-314.3(846.)]TJ
20.374 -0.4714 TD
[(lated)-314.3(to)-314.3(human)-314.3(bone)-314.3(morphogenetic)-314.3(pr)14.3(otein)-314.3(1.)-314.3(Cell)]TJ
/F5 1 Tf
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(67)Tj
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[(,)-314.3(469481.)]TJ
-59.4584 -1.1714 TD
[(Lander)85.7(,)-242.9(A.D.,)-257.1(Nie,)-242.9(Q.,)-257.1(and)-242.8(W)42.9(an,)-242.9(F)128.6(.)0(Y)114.3(.)-257.1(\(2002\).)-242.9(Do)-257.1(morphogen)-242.9(gradients)]TJ
34.2857 -0.4143 TD
[(Shimmi,)-342.8(O.,)-328.6(and)-342.8(OConnor)85.7(,)-328.6(M.B.)-342.9(\(2003\).)-328.6(Physical)-342.9(pr)14.3(operties)-328.6(of)-342.8(Tld,)]TJ
-34.2857 -0.8714 TD
[(arise)-314.3(by)-314.3(dif)14.3(fusion?)-314.3(Dev)71.4(.)-314.3(Cell)]TJ
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(2)Tj
/F3 1 Tf
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[(,)-314.3(785796.)]TJ
20.5162 -0.4143 TD
[(Sog,)-314.3(T)114.3(s)0(g)-314.3(and)-314.3(Dpp)-314.3(pr)14.3(otein)-300(interactions)-314.3(ar)14.3(e)-314.3(p)0(r)14.3(edicted)-314.3(to)-314.3(help)-314.3(cr)14.3(eate)]TJ
-34.2857 -1.2286 TD
[(Lander)85.7(,)-371.4(A.D.,)-371.4(Nie,)-371.4(Q.,)-371.4(and)-385.7(W)42.9(an,)-371.4(F)128.6(.)0(Y)114.3(.M.)-371.4(\(2005\).)-371.4(Spatially)-371.4(distributed)]TJ
34.2857 -0.0571 TD
[(a)-300(sharp)-300(boundary)-285.7(in)-300(Bmp)-300(signals)-300(during)-285.7(dorsoventral)-300(patter)-14.3(ning)-300(of)]TJ
-34.2857 -1.2286 TD
[(morphogen)-500(synthesis)-500(and)-485.7(morphogen)-500(gradient)-500(formation.)-500(Math.)]TJ
34.2857 -0.0571 TD
(the)Tj
/F5 1 Tf
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(Drosophila)Tj
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[(embryo.)-314.3(Development)]TJ
/F5 1 Tf
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(130)Tj
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[(,)-314.3(46734682.)]TJ
-53.5846 -1.2286 TD
[(Biosci.)-314.3(Eng.)]TJ
/F5 1 Tf
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(2)Tj
/F3 1 Tf
0.556 0 TD
[(,)-314.3(239262.)]TJ
27.8942 -0.3571 TD
[(Shimmi,)-271.4(O.,)-285.7(Umulis,)-271.4(D.,)-271.4(Othmer)85.7(,)-271.4(H.,)-285.7(and)-271.4(OConnor)85.7(,)-271.4(M)0(.)-285.7(\(2005\).)-271.4(Facili-)]TJ
0 -1.2857 TD
[(tated)-300(transport)-300(of)-314.3(a)-300(Dpp/Scw)-300(heter)14.3(odimer)-300(by)-314.3(Sog/T)114.3(sg)-300(patter)-14.3(ns)-300(the)]TJ
-34.2857 0 TD
[(Lecuit,)-371.4(T)114.3(.)0(,)-371.4(and)-371.4(Cohen,)-371.4(S.M.)-357.1(\(1998\).)-371.4(Dpp)-371.4(r)14.3(eceptor)-371.4(levels)-371.4(contribute)]TJ
0 -1.2857 TD
[(to)-471.4(shaping)-471.4(the)-471.4(Dpp)-471.4(morphogen)-485.7(gradient)-471.4(in)-471.4(the)]TJ
/F5 1 Tf
23.1964 0 TD
(Drosophila)Tj
/F3 1 Tf
5.4724 0 TD
[(wing)-3430.9(dorsal)-557.1(surface)-557.1(of)-557.1(the)]TJ
/F5 1 Tf
16.5164 0 TD
(Drosophila)Tj
/F3 1 Tf
5.5581 0 TD
[(blastoderm)-557.1(embryo.)-557.1(Cell)]TJ
/F5 1 Tf
12.4523 0 TD
(120)Tj
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1.668 0 TD
(,)Tj
-30.5778 -1.2857 TD
(873886.)Tj
-34.2857 0 TD
[(imaginal)-314.3(disc.)-314.3(Development)]TJ
/F5 1 Tf
13.1507 0 TD
(125)Tj
/F3 1 Tf
1.668 0 TD
[(,)-314.3(49014907.)]TJ
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