Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Development. 2010 Aug;137(16):2691-701. doi: 10.1242/dev.050096. Epub 2010 Jul 7.
The development of neural crest cells involves an epithelial-mesenchymal transition (EMT) associated with the restriction of cadherin 6B expression to the pre-migratory neural crest cells (PMNCCs), as well as a loss of N-cadherin expression. We find that cadherin 6B, which is highly expressed in PMNCCs, persists in early migrating neural crest cells and is required for their emigration from the neural tube. Cadherin 6B-expressing PMNCCs exhibit a general loss of epithelial junctional polarity and acquire motile properties before their delamination from the neuroepithelium. Cadherin 6B selectively induces the de-epithelialization of PMNCCs, which is mediated by stimulation of BMP signaling, whereas N-cadherin inhibits de-epithelialization and BMP signaling. As BMP signaling also induces cadherin 6B expression and represses N-cadherin, cadherin-regulated BMP signaling may create two opposing feedback loops. Thus, the overall EMT of neural crest cells occurs via two distinct steps: a cadherin 6B and BMP signaling-mediated de-epithelialization, and a subsequent delamination through the basement membrane.
神经嵴细胞的发育涉及上皮-间充质转化（EMT），伴随着钙黏蛋白 6B 表达的限制到前迁移神经嵴细胞（PMNCCs），以及 N-钙黏蛋白表达的丧失。我们发现，高度表达于 PMNCCs 的钙黏蛋白 6B 持续存在于早期迁移的神经嵴细胞中，并对其从神经管中迁出是必需的。钙黏蛋白 6B 表达的 PMNCCs 在从神经上皮层分离之前表现出上皮连接极性的普遍丧失，并获得运动性。钙黏蛋白 6B 通过刺激 BMP 信号选择性诱导 PMNCCs 的去上皮化，而 N-钙黏蛋白抑制去上皮化和 BMP 信号。由于 BMP 信号也诱导钙黏蛋白 6B 的表达并抑制 N-钙黏蛋白，钙黏蛋白调节的 BMP 信号可能产生两个相反的反馈环。因此，神经嵴细胞的整体 EMT 通过两个不同的步骤发生：钙黏蛋白 6B 和 BMP 信号介导的去上皮化，以及随后通过基膜的分层。
