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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The zebrafish homologue of mammalian chimerin Rac-GAPs is implicated in epiboly progression during development
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The zebrafish homologue of mammalian chimerin Rac-GAPs is implicated in epiboly progression during development

机译：哺乳动物嵌合蛋白Rac-GAPs的斑马鱼同源物参与发育过程中的外延进展

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In this paper, we report an in vivo model for the chimerins, a family of Rac GTPase-activating proteins (Rac-GAPs) that are uniquely regulated by the lipid second messenger diacylglycerol and have been implicated in the control of actin dynamics, migration, and proliferation. We cloned the zebrafish homologue of mammalian alpha 2-chimerin (chn1) and determined that it possesses Rac-GAP activity and a C1 domain with phorbol ester/diacylglycerol-binding capability. chn1 morpholino knockdown embryos exhibit severe abnormalities, including the development of round somites, lack of yolk extension, and a kinked posterior notochord. These zebrafish morphants show Rac hyperactivation and progress faster through epiboly, leading to tailbud-stage embryos that have a narrow axis and an enlarged tailbud with expanded bmp4 and shh expression. Phenotypic rescue was achieved by mRNA microinjection of chn1 or an active chimerin Rac-GAP domain into the yolk syncytial layer but not by a chn1 mutant deficient in Rac-GAP activity, suggesting that the lack of chn1 Rac-GAP activity in the yolk syncytial layer was causative of the misbalance in morphogenetic movements. Our results reveal a crucial role for chn1 in early development and implicate Rac as a key regulator of morphogenetic movements during zebrafish epiboly.
机译：在本文中，我们报告了嵌合蛋白的体内模型，该嵌合蛋白是Rac GTPase激活蛋白（Rac-GAP）家族，受脂质第二信使二酰基甘油的独特调控，并参与了肌动蛋白动力学，迁移，和扩散。我们克隆了哺乳动物的α2-嵌合蛋白（chn1）的斑马鱼同源物，并确定它具有Rac-GAP活性和具有佛波酯/二酰甘油结合能力的C1域。 chn1吗啉代敲低的胚胎表现出严重的异常，包括圆形卵节的发育，卵黄延伸的缺乏和后脊索的扭结。这些斑马鱼的变体表现出Rac过度激活，并通过表皮发育更快，导致尾轴阶段的胚胎具有狭窄的轴和扩大的bmp4和shh表达的尾巴。表型抢救是通过将chn1或有活性的嵌合Rac-GAP结构域mRNA显微注射到卵黄合胞体层中实现的，但不是通过缺乏Rac-GAP活性的chn1突变体实现的，这表明卵黄合胞体层中缺乏chn1 Rac-GAP活性是形态发生运动失衡的原因。我们的研究结果揭示了chn1在早期发育中的关键作用，并暗示Rac作为斑马鱼外突期间形态发生运动的关键调节剂。

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