Cadherin-11 Is Required for Neural Crest Specification and Survival.
Cadherin-11 Is Required for Neural Crest Specification and Survival.
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DOI：
10.3389/fphys.2020.563372
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发表时间：
2020
影响因子：
4
通讯作者：
Rogers CD
中科院分区：
文献类型：
--
作者：
Manohar S;Camacho-Magallanes A;Echeverria C Jr;Rogers CD
神经嵴（NC）细胞是多能胚胎细胞，形成黑素细胞、颅面骨和软骨以及脊椎动物的周围神经系统。NC细胞表达许多钙粘蛋白，其控制其特化、上皮向间充质转化（EMT）、迁移和间充质向上皮转化。NC发育异常导致先天性缺陷，包括颅面裂以及NC衍生的癌症。在这里，我们确定了II型钙粘蛋白，钙粘蛋白-11（CDH 11），在早期鸡NC发展的作用。已知CDH 11在两栖动物胚胎中的NC细胞迁移以及癌细胞中的细胞存活、增殖和迁移中起作用。它也与人类的复杂神经嵴髓病疾病Elsahy-Waters综合征有关。在这项研究中，我们敲低CDH 11的翻译开始时，其表达在NC域在NC诱导。CDH 11的缺失导致背侧神经管中真正的NC细胞减少，并伴有细胞存活和迁移的缺陷。CDH 11的缺失增加了p53介导的程序性细胞死亡，阻断p53通路拯救了NC表型。我们的研究结果揭示了在NC发展的早期需要CDH 11，并证明了调节NC发展的机制的复杂性，其中单个细胞-细胞粘附蛋白同时控制多个基本的细胞功能，以确保适当的规格，生存和过渡到背神经管中的迁移阶段。我们的研究结果也可能增加我们对早期钙粘蛋白相关的NC发育缺陷的理解。
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 known to play a role in NC cell migration in amphibian embryos as well as cell survival, proliferation, and migration in cancer cells. It has also been linked to the complex neurocristopathy disorder, Elsahy-Waters Syndrome, in humans. In this study, we knocked down CDH11 translation at the onset of its expression in the NC domain during NC induction. Loss of CDH11 led to a reduction of bonafide NC cells in the dorsal neural tube combined with defects in cell survival and migration. Loss of CDH11 increased p53-mediated programmed-cell death, and blocking the p53 pathway rescued the NC phenotype. Our findings reveal an early requirement for CDH11 in NC development and demonstrated the complexity of the mechanisms that regulate NC development, where a single cell-cell adhesion protein simultaneous controls multiple essential cellular functions to ensure proper specification, survival, and transition to a migratory phase in the dorsal neural tube. Our findings may also increase our understanding of early cadherin-related NC developmental defects.
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