Regulation of cell protrusions by small GTPases during fusion of the neural folds.
Regulation of cell protrusions by small GTPases during fusion of the neural folds.
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DOI：
10.7554/elife.13273
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发表时间：
2016-04-26
期刊：
影响因子：
7.7
通讯作者：
Copp AJ
中科院分区：
文献类型：
--
作者：
Rolo A;Savery D;Escuin S;de Castro SC;Armer HE;Munro PM;Molè MA;Greene ND;Copp AJ
上皮融合是胚胎发育的关键过程，其失败是几种临床上重要的出生缺陷的基础。例如，神经形成期间神经褶融合的失败导致开放性神经管缺陷，包括脊柱裂。使用小鼠胚胎，我们表明，从并列的神经褶皱尖端，在神经上皮细胞和表面外胚层之间的接口，所需的细胞突起完成神经管关闭。通过基因消融的细胞骨架调节Rac 1或Cdc 42在背神经上皮，或在表面外胚层，我们表明，这些突起起源于表面外胚层细胞和Rac 1是必要的膜皱褶的形成，代表后期关闭阶段，而Cdc 42所需的优势丝状伪足在早期神经胚。本研究为哺乳动物发育中重要器官原基融合前膜突起的重要作用和分子调控提供了证据。http://dx.doi.org/10.7554/eLife.13273.001神经管是一种胚胎结构，它产生大脑和脊髓。它起源于一片扁平的细胞-神经板-在发育过程中卷起并融合形成一个管。如果这种闭合失败，就会导致出生缺陷，如脊柱裂，这种情况会导致严重残疾，因为婴儿出生时脊髓暴露和受损。当神经板的边缘相遇时，它们需要融合在一起以产生一个封闭的管道。已知这些边缘处的细胞延伸突起。然而，目前还不清楚这些突起是如何调节的，它们是来自神经细胞还是非神经细胞，以及它们是否是神经管完全关闭所必需的。通过研究突变小鼠胚胎，Rolo等人发现，细胞突起确实是神经管完全闭合所必需的。这些突起被证明是由称为Rac 1和Cdc 42的蛋白质调节的，这些蛋白质控制着细胞内负责细胞形状和运动的细丝。Rolo等人还发现，产生突起的细胞不是神经板本身的一部分。相反，这些细胞是来自后来形成皮肤表皮（表面外胚层）的层的相邻细胞。未来的研究将需要调查哪些信号指示这些精确的细胞产生突起，并发现突起与另一侧的细胞接触后发生了什么。这也将是重要的，以确定是否脊柱裂可能会出现在人类，如果突起是有缺陷的或没有。DOI：http://dx.doi.org/10.7554/eLife.13273.002网站
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. DOI: http://dx.doi.org/10.7554/eLife.13273.001 The neural tube is an embryonic structure that gives rise to the brain and spinal cord. It originates from a flat sheet of cells – the neural plate – that rolls up and fuses to form a tube during development. If this closure fails, it leads to birth defects such as spina bifida, a condition that causes severe disability because babies are born with an exposed and damaged spinal cord. As the edges of the neural plate meet, they need to fuse together to produce a closed tube. It was known that cells at these edges extend protrusions. However, it was unclear how these protrusions are regulated, whether they arise from neural or non-neural cells and whether or not they are required for the neural tube to close fully. By studying mutant mouse embryos, Rolo et al. found that cellular protrusions are indeed required for the neural tube to close completely. These protrusions proved to be regulated by proteins called Rac1 and Cdc42, which control the filaments inside the cell that are responsible for cell shape and movement. Rolo et al. also found that the cells that give rise to the protrusions are not part of the neural plate itself. Instead, these cells are neighboring cells from the layer that later forms the epidermis of the skin (the surface ectoderm). Future studies will need to investigate which signals instruct those precise cells to make protrusions and to discover what happens to the protrusions after contact is made with cells on the opposite side. It will also be important to determine whether spina bifida may arise in humans if the protrusions are defective or absent. DOI: http://dx.doi.org/10.7554/eLife.13273.002