title: Requirement of FoxD3-class signaling for neural crest determination in Xenopus.
abstract: Fox factors (winged-helix transcription factors) play important roles in early embryonic patterning. We show here that FoxD3 (Forkhead 6) regulates neural crest determination in Xenopus embryos. Expression of FoxD3 in the presumptive neural crest region starts at the late gastrula stage in a manner similar to that of Slug, and overlaps with that of Zic-r1. When overexpressed in the embryo and in ectodermal explants, FoxD3 induces expression of neural crest markers. Attenuation of FoxD3-related signaling by a dominant-negative FoxD3 construct (FoxD3delN) inhibits neural crest differentiation in vivo without suppressing the CNS marker Sox2. Interestingly, these loss-of-function phenotypes are reversed by coinjecting SLUG: In animal cap explants, neural crest differentiation induced by Slug and Wnt3a is also inhibited by FoxD3delN but not by a dominant-negative form of XBF2. Loss-of-function studies using dominant-negative forms of FoxD3 and Slug indicate that Slug induction by Zic factors requires FoxD3-related signaling, and that FoxD3 and Slug have different requirements in inducing downstream neural crest markers. These data demonstrate that FoxD3 (or its closely related factor) is an essential upstream regulator of neural crest determination.
authors.affiliation: Department of Medical Embryology and Neurobiology, and. Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo, Kyoto 606-8507, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sasai
authors.forename: K
authors.initials: K
authors.lastname: Mizuseki
authors.forename: Y
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004475:Ectoderm; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D015415:Biomarkers; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C491001:FOXL1 protein, human; D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C491003:foxd3b-A protein, Xenopus