title: Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos.
abstract: Defining which key factors control commitment of an embryonic lineage among a myriad of candidates is a longstanding challenge in developmental biology and an essential prerequisite for developing stem cell-based therapies. Commitment implies that the induced cells not only express early lineage markers but further undergo an autonomous differentiation into the lineage. The embryonic neural crest generates a highly diverse array of derivatives, including melanocytes, neurons, glia, cartilage, mesenchyme, and bone. A complex gene regulatory network has recently classified genes involved in the many steps of neural crest induction, specification, migration, and differentiation. However, which factor or combination of factors is sufficient to trigger full commitment of this multipotent lineage remains unknown. Here, we show that, in contrast to other potential combinations of candidate factors, coactivating transcription factors Pax3 and Zic1 not only initiate neural crest specification from various early embryonic lineages in Xenopus and chicken embryos but also trigger full neural crest determination. These two factors are sufficient to drive migration and differentiation of several neural crest derivatives in minimal culture conditions in vitro or ectopic locations in vivo. After transplantation, the induced cells migrate to and integrate into normal neural crest craniofacial target territories, indicating an efficient spatial recognition in vivo. Thus, Pax3 and Zic1 cooperate and execute a transcriptional switch sufficient to activate full multipotent neural crest development and differentiation.
authors.affiliation: Institut Curie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 3347, Institut National de la Santé et de la Recherche Médicale U1021, F-91405 Orsay Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Milet
authors.forename: Frédérique
authors.initials: F
authors.lastname: Maczkowiak
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Roche
authors.forename: Anne Hélène
authors.initials: AH
authors.lastname: Monsoro-Burq
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D017931:DNA Primers / Q000235:genetics; D018274:Electroporation; D053263:Gene Regulatory Networks / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018715:Microscopy, Video; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C489411:Pax3 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; C116546:Zic1 protein, Xenopus