Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction.
FGF, WNT, and BMP signaling promote neural crest formation at the neural plate boundary in vertebrate embryos. To understand how these signals are integrated, we have analyzed the role of the transcription factors Msx1 and Pax3. Using a combination of overexpression and morpholino-mediated knockdown strategies in Xenopus, we show that Msx1 and Pax3 are both required for neural crest formation, display overlapping but nonidentical activities, and that Pax3 acts downstream of Msx1. In neuralized ectoderm, Msx1 is sufficient to induce multiple early neural crest genes. Msx1 induces Pax3 and ZicR1 cell autonomously, in turn, Pax3 combined with ZicR1 activates Slug in a WNT-dependent manner. Upstream of this, WNTs initiate Slug induction through Pax3 activity, whereas FGF8 induces neural crest through both Msx1 and Pax3 activities. Thus, WNT and FGF8 signals act in parallel at the neural border and converge on Pax3 activity during neural crest induction.
Monsoro-Burq
Anne-Hélène
AH
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. anne-helene.monsoro-burq@curie.u-psud.fr
Wang
Estee
E
Harland
Richard
R
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004627:Embryonic Induction / Q000235:genetics / Q000502:physiology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051957:MSX1 Transcription Factor; D008954:Models, Biological; D009432:Neural Crest / Q000196:embryology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051957:MSX1 Transcription Factor; C497996:MSX1 protein, Xenopus; D020319:Oligodeoxyribonucleotides, Antisense; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C489411:Pax3 protein, Xenopus; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors