Specification of the neural crest occurs during gastrulation and requires Pax7
Specification of the neural crest occurs during gastrulation and requires Pax7
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DOI：
10.1038/nature04684
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发表时间：
2006-05-11
期刊：
影响因子：
64.8
通讯作者：
García-Castro, MI
中科院分区：
文献类型：
--
作者：
Basch, ML;Bronner-Fraser, M;García-Castro, MI
神经嵴是脊椎动物颅面骨骼和外周神经节发育的关键干细胞群。神经嵴细胞沿着神经板和表皮之间的边界起源（1），广泛迁移并产生许多衍生物，包括周围神经系统的神经元和神经胶质、黑素细胞、头部骨骼的骨和软骨（2）。神经嵴发育受损与人类缺陷有关，包括腭裂（3）。传统上，神经嵴被认为是通过在神经和非神经外胚层或中胚层之间的边界处的相互作用形成的（4-7），并且已确定的因子如骨形态发生蛋白（BMP）和Wnt蛋白被假定为神经嵴诱导剂（8-13）。虽然诱导嵴细胞的能力在第10阶段后下降（参考文献14），但对体内神经嵴诱导何时开始知之甚少。在这里，我们报告说，神经嵴诱导正在进行中原肠胚形成和正确的神经板外观之前。我们表明，鸡上胚层（阶段3 - 4）的一个限制性区域被指定为产生神经嵴细胞时，在非诱导条件下的recruted。该区域在第41期表达转录因子Pax 7，随后有助于神经褶皱和迁移神经嵴。在鸡胚胎中，Pax 7是体内神经嵴形成所必需的，因为阻断其翻译会抑制神经嵴标志物Slug、Sox 9、Sox 10和HNK-1的表达。我们的研究结果表明，神经嵴规格启动早于以前假设的，独立的中胚层和神经组织，和Pax 7神经嵴发育过程中有一个至关重要的功能。
The neural crest is a stem population critical for development of the vertebrate craniofacial skeleton and peripheral ganglia. Neural crest cells originate along the border between the neural plate and epidermis(1), migrate extensively and generate numerous derivatives, including neurons and glia of the peripheral nervous system, melanocytes, bone and cartilage of the head skeleton(2). Impaired neural crest development is associated with human defects, including cleft palate(3). Classically, the neural crest has been thought to form by interactions at the border between neural and non-neural ectoderm or mesoderm(4-7), and defined factors such as bone morphogenetic proteins (BMPs) and Wnt proteins have been postulated as neural crest-inducers(8-13). Although competence to induce crest cells declines after stage 10 ( ref. 14), little is known about when neural crest induction begins in vivo. Here we report that neural crest induction is underway during gastrulation and well before proper neural plate appearance. We show that a restricted region of chick epiblast ( stage 3 - 4) is specified to generate neural crest cells when explanted under non-inducing conditions. This region expresses the transcription factor Pax7 by stage 41 and later contributes to neural folds and migrating neural crest. In chicken embryos, Pax7 is required for neural crest formation in vivo, because blocking its translation inhibits expression of the neural crest markers Slug, Sox9, Sox10 and HNK-1. Our results indicate that neural crest specification initiates earlier than previously assumed, independently of mesodermal and neural tissues, and that Pax7 has a crucial function during neural crest development.