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XB-ART-46797
Proc Natl Acad Sci U S A April 2, 2013; 110 (14): 5528-33.

Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos.

Milet C , Maczkowiak F , Roche DD , Monsoro-Burq AH .


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.

PubMed ID: 23509273
PMC ID: PMC3619367
Article link: Proc Natl Acad Sci U S A

Genes referenced: actl6a cdh1 cdh2 eef1a2 ets1 etv2 fn1 foxd3 gal.2 h2bc21 hes4 id3 mrc1 msx1 myc pax3 runx2 snai1 snai2 sox10 sox8 sox9 tfap2a th twist1 zic1 zic5


Article Images: [+] show captions
References [+] :
Aybar, Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. 2002, Pubmed, Xenbase


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