Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a.
Members of the Wnt family of signaling molecules are expressed differentially along the dorsal-ventral axis of the developing neural tube. Thus we asked whether Wnt factors are involved in patterning of the nervous system along this axis. We show that Wnt-1 and Wnt-3a, both of which are expressed in the dorsal portion of the neural tube, could synergize with the neural inducers noggin and chordin in Xenopus animal explants to generate the most dorsal neural structure, the neural crest, as determined by the expression of Krox-20, AP-2, and slug. Overexpression of Wnt-1 or Wnt-3a in the neuroectoderm of whole embryos led to a dramatic increase of slug and Krox-20-expressing cells, but the hindbrain expression of Krox-20 remained unaffected. Enlargement in the neural crest population could occur even when cell proliferation was inhibited. Wnt-5A and Wnt-8, neither of which is expressed in the dorsal neuroectoderm, failed to induce neural crest markers. Overexpression of glycogen synthase kinase 3, known to antagonize Wnt signaling, blocked the neural-crest-inducing activity of Wnt-3a in animal explants and inhibited neural crest formation in whole embryos. We suggest that Wnt-1 and Wnt-3a have a role in patterning the neural tube along its dorsoventral axis and function in the differentiation of the neural crest.
Saint-Jeannet
J P
JP
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
He
X
X
Varmus
H E
HE
Dawid
I B
IB
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051767:Early Growth Response Protein 2; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D005819:Genetic Markers; D011506:Proteins; D011518:Proto-Oncogene Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C495249:WNT1 protein, Xenopus; C495247:WNT1 protein, human; C555506:WNT3A protein, Xenopus; C555510:WNT3A protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C495248:wnt8a protein, Xenopus; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3