Betters Erin, Charney Rebekah M, Garcia-Castro Martín I
School of Medicine Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
School of Medicine Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Dev Biol. 2018 Dec 1;444 Suppl 1(Suppl 1):S181-S192. doi: 10.1016/j.ydbio.2018.06.012. Epub 2018 Jun 20.
The phenomenal migratory and differentiation capacity of neural crest cells has been well established across model organisms. While the earliest stages of neural crest development have been investigated in non-mammalian model systems such as Xenopus and Aves, the early specification of this cell population has not been evaluated in mammalian embryos, of which the murine model is the most prevalent. Towards a more comprehensive understanding of mammalian neural crest formation and human comparative studies, we have used the rabbit as a mammalian system for the study of early neural crest specification and development. We examine the expression profile of well-characterized neural crest markers in rabbit embryos across developmental time from early gastrula to later neurula stages, and provide a comparison to markers of migratory neural crest in the chick. Importantly, we apply explant specification assays to address the pivotal question of mammalian neural crest ontogeny, and provide the first evidence that a specified population of neural crest cells exists in the rabbit gastrula prior to the overt expression of neural crest markers. Finally, we demonstrate that FGF signaling is necessary for early rabbit neural crest formation, as SU5402 treatment strongly represses neural crest marker expression in explant assays. This study pioneers the rabbit as a model for neural crest development, and provides the first demonstration of mammalian neural crest specification and the requirement of FGF signaling in this process.
神经嵴细胞显著的迁移和分化能力在各种模式生物中已得到充分证实。虽然神经嵴发育的最早阶段已在非洲爪蟾和鸟类等非哺乳动物模式系统中进行了研究，但在哺乳动物胚胎中尚未评估这一细胞群体的早期特化，其中小鼠模型最为普遍。为了更全面地了解哺乳动物神经嵴的形成以及人类比较研究，我们将兔子作为一种哺乳动物系统来研究神经嵴的早期特化和发育。我们检测了从早期原肠胚到后期神经胚阶段发育过程中兔子胚胎中特征明确的神经嵴标志物的表达谱，并与鸡中迁移神经嵴的标志物进行了比较。重要的是，我们应用外植体特化分析来解决哺乳动物神经嵴个体发生的关键问题，并提供了首个证据，即在神经嵴标志物明显表达之前，兔子原肠胚中存在特定群体的神经嵴细胞。最后，我们证明FGF信号对于早期兔子神经嵴的形成是必需的，因为在体外分析中，SU5402处理强烈抑制神经嵴标志物的表达。本研究开创了将兔子作为神经嵴发育模型的先河，并首次证明了哺乳动物神经嵴的特化以及该过程中FGF信号的需求。
