Sanchez-Ferras Oraly, Bernas Guillaume, Farnos Omar, Touré Aboubacrine M, Souchkova Ouliana, Pilon Nicolas
Molecular Genetics of Development Laboratory, Department of Biological Sciences and BioMed Research Center, University of Quebec at Montreal (UQAM), Montreal H2X 3Y7, Canada.
Molecular Genetics of Development Laboratory, Department of Biological Sciences and BioMed Research Center, University of Quebec at Montreal (UQAM), Montreal H2X 3Y7, Canada
Development. 2016 Apr 15;143(8):1363-74. doi: 10.1242/dev.132159. Epub 2016 Mar 7.
Numerous studies in chordates and arthropods currently indicate that Cdx proteins have a major ancestral role in the organization of post-head tissues. In urochordate embryos, Cdx loss-of-function has been shown to impair axial elongation, neural tube (NT) closure and pigment cell development. Intriguingly, in contrast to axial elongation and NT closure, a Cdx role in neural crest (NC)-derived melanocyte/pigment cell development has not been reported in any other chordate species. To address this, we generated a new conditional pan-Cdx functional knockdown mouse model that circumvents Cdx functional redundancy as well as the early embryonic lethality of Cdx mutants. Through directed inhibition in the neuroectoderm, we provide in vivo evidence that murine Cdx proteins impact melanocyte and enteric nervous system development by, at least in part, directly controlling the expression of the key early regulators of NC ontogenesis Pax3,Msx1 and Foxd3 Our work thus reveals a novel role for Cdx proteins at the top of the trunk NC gene regulatory network in the mouse, which appears to have been inherited from their ancestral ortholog.
目前，在脊索动物和节肢动物中进行的大量研究表明，Cdx蛋白在头部后组织的组织过程中具有主要的祖先作用。在尾索动物胚胎中，已证明Cdx功能丧失会损害轴向伸长、神经管（NT）闭合和色素细胞发育。有趣的是，与轴向伸长和NT闭合相反，在任何其他脊索动物物种中均未报道Cdx在神经嵴（NC）衍生的黑素细胞/色素细胞发育中的作用。为了解决这个问题，我们生成了一种新的条件性泛Cdx功能敲低小鼠模型，该模型规避了Cdx功能冗余以及Cdx突变体的早期胚胎致死性。通过在神经外胚层中的定向抑制，我们提供了体内证据，证明小鼠Cdx蛋白至少部分地通过直接控制NC发生的关键早期调节因子Pax3、Msx1和Foxd3的表达来影响黑素细胞和肠神经系统的发育。因此，我们的工作揭示了Cdx蛋白在小鼠躯干NC基因调控网络顶端的新作用，这一作用似乎是从它们的祖先直系同源基因继承而来的。
