Data from: Regulation of cell protrusions by small GTPases during fusion of the neural folds

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development.上皮融合是胚胎发育中的关键过程，其功能异常是多种临床意义重大的出生缺陷的致病基础。例如，神经胚形成过程中神经褶融合失败，会引发包括脊柱裂在内的开放性神经管缺陷。本研究以小鼠胚胎为模型，证实位于神经上皮与表面外胚层交界处的、由相互靠拢的神经褶尖端所伸出的细胞突起，对于神经管闭合的完成是必需的。通过在背侧神经上皮或表面外胚层中对细胞骨架调控因子Rac1或Cdc42进行基因消融，本研究证实这些细胞突起源自表面外胚层细胞；同时发现，Rac1对于神经闭合晚期标志性的膜皱褶形成不可或缺，而Cdc42则是神经胚形成早期丝状伪足占主导所必需的。本研究为哺乳动物发育过程中关键器官原基融合前的细胞突起的必需作用及其分子调控机制提供了实验证据。