title: The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate.
abstract: The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Dottori
authors.forename: M K
authors.initials: MK
authors.lastname: Gross
authors.forename: P
authors.initials: P
authors.lastname: Labosky
authors.forename: M
authors.initials: M
authors.lastname: Goulding
mesh_terms: D000818:Animals; D030161:Avian Proteins; D015415:Biomarkers; D018959:CD57 Antigens / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004627:Embryonic Induction / Q000235:genetics; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D019077:Helix-Turn-Helix Motifs; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013116:Spinal Cord / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000235:genetics
chemical_list: D030161:Avian Proteins; D015415:Biomarkers; D018959:CD57 Antigens; C094294:Cad7 protein, Gallus gallus; D015820:Cadherins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D020743:rhoB GTP-Binding Protein