Xenopus fibrillin regulates directed convergence and extension
Xenopus fibrillin regulates directed convergence and extension
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DOI：
10.1016/j.ydbio.2006.09.005
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发表时间：
2007-01-15
影响因子：
2.7
通讯作者：
Keller, Ray
中科院分区：
文献类型：
--
作者：
Skoglund, Paul;Keller, Ray
原纤维蛋白为基础的人类疾病，如马凡氏综合征和先天性挛缩性蛛网膜炎牵连原纤维蛋白的功能和稳态的多个成人组织。原纤蛋白也在胚胎中表达，但这些蛋白质没有描述早期发育作用。我们使用三种独立的方法来揭示非洲爪蟾卵蛋白（XF）在原肠胚形成的作用。首先，在胚胎中表达截短形式的XF导致原肠胚形成的失败，伴随着对天然大肠杆菌蛋白原纤维组装的显性负效应。表达截短的XF还抑制图案化的极化细胞运动的正常进展，所述运动驱动原肠胚形成时的会聚和延伸，并干扰背中胚层的培养外植体中的定向延伸。第二，注射一种合成肽编码的细胞结合结构域的XF到midgastrula胚胎引起急性失败的原肠胚与缺陷的肠蛋白原纤维组装。这些注射也揭示了这种肽在原纤维组装过程中的关键作用。第三，吗啉代介导的XF在胚胎中的翻译敲低也扰乱了正常的原肠胚形成和定向延伸。总之，这些数据表明，本地非洲爪蟾蛋白是必不可少的过程中，在原肠形成推定脊索定向收敛延伸。(c)2006年爱思唯尔公司All rights reserved.
Fibrillin-based human diseases such as Marfan syndrome and congenital contractural arachnodactyly implicate fibrillins in the function and homeostasis of multiple adult tissues. Fibrillins are also expressed in embryos, but no early developmental role has been described for these proteins. We use three independent methods to reveal a role for Xenopus fibrillin (XF) at gastrulation. First, expressing truncated forms of XF in the embryo leads to failure of gastrulation concomitant with a dominant-negative effect on native fibrillin fibril assembly. Expressing truncated XF also inhibits normal progression of the patterned, polarized cell motility that drives convergence and extension at gastrulation and perturbs directed extension in cultured explants of dorsal mesoderm. Second, injection of a synthetic peptide encoding a cell-binding domain of XF into midgastrula embryos causes acute failure of gastrulation associated with defective fibrillin fibril assembly. These injections also reveal a critical role for this peptide in the fibril assembly process. Third, morpholino-mediated knockdown of translation of XF in the embryo also perturbs normal gastrulation and directed extension. Together, these data show that native Xenopus fibrillin is essential for the process of directed convergent extension in presumptive notochord at gastrulation. (c) 2006 Elsevier Inc. All rights reserved.