Neural crest (NC) cells are multipotent embryonic cells that form melanocytes, craniofacial bone and cartilage, and the peripheral nervous system in vertebrates. NC cells express many cadherin proteins, which control their specification, epithelial to mesenchymal transition (EMT), migration, and mesenchymal to epithelial transition. Abnormal NC development leads to congenital defects including craniofacial clefts as well as NC-derived cancers. Here, we identify the role of the type II cadherin protein, Cadherin-11 (CDH11), in early chicken NC development. CDH11 is crucial for NC cell migration in amphibian embryos and is linked to cell survival, proliferation, and migration in cancer cells. It has been linked to the complex neurocristopathy disorder, Elsahy‐Waters Syndrome, in humans. Using immunohistochemistry (IHC), we determined that CDH11 protein has dynamic expression that is first co-localized with neural progenitors in early embryos and subsequently upregulated specifically in NC cells as they are specified in the dorsal neural tube prior to migration. We identified that loss of CDH11 led to a reduction of bonafide NC cells in the dorsal neural tube combined with defects in cell migration and survival. Loss of CDH11 increased p53-mediated programmed-cell death, and blocking the p53 pathway rescued the NC phenotype. Our findings demonstrate an early requirement for CDH11 in NC development, and may increase our understanding of early cadherin-related NC developmental defects.

中文翻译：

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Cadherin-11是确定神经determination和存活所必需的

神经c（NC）细胞是形成胚胎中黑素细胞，颅面骨和软骨以及外周神经系统的多能胚胎细胞。NC细胞表达许多钙粘蛋白蛋白，这些蛋白控制着它们的规格，上皮向间质转化（EMT），迁移以及间质向上皮转化。NC异常发展会导致先天性缺陷，包括颅面裂以及NC衍生的癌症。在这里，我们确定II型钙粘蛋白Cadherin-11（CDH11）在早期鸡NC发育中的作用。CDH11对于两栖动物胚胎中NC细胞的迁移至关重要，并与癌细胞的细胞存活，增殖和迁移有关。它已与人类复杂的神经病变（Elsahy-Waters综合征）相关。使用免疫组织化学（IHC），我们确定CDH11蛋白具有动态表达，该蛋白首先与早期胚胎中的神经祖细胞共定位，然后如在迁移前在背神经管中指定的那样，在NC细胞中特异上调。我们发现，CDH11的缺失导致背神经管中的真正NC细胞减少，并伴有细胞迁移和存活的缺陷。CDH11的丢失增加了p53介导的程序性细胞死亡，并且阻断p53途径可以挽救NC表型。我们的研究结果表明CDH11在NC发展中的早期需求，并可能增加我们对与钙粘蛋白相关的NC发展早期缺陷的了解。