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首页> 外文学位 >Characterization of a Cdc42 effector protein (Cep4l) and a novel role for Cdc42 in Xenopus neurogenesis and Fgf signaling.
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Characterization of a Cdc42 effector protein (Cep4l) and a novel role for Cdc42 in Xenopus neurogenesis and Fgf signaling.

机译：Cdc42效应蛋白（Cep41）的表征以及Cdc42在非洲爪蟾神经发生和Fgf信号转导中的新作用。

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摘要

The vegetal cortex of the Xenopus oocyte is enriched for several mRNAs critical for early embryonic developmental processes, including germ layer specification and dorsoventral axis formation. A recent microarray screen for other vegetally localized RNAs identified several hundred novel cortex-enriched transcripts, which may have undiscovered roles in early development. In order to better elucidate the functions of localized mRNAs in early development, I characterized the spatiotemporal expression patterns and developmental functions of two novel transcripts, TRIO and F-actin binding protein ( triobp) and Cdc42 effector protein 4-like (cep4l).;Overexpression and loss-of-function experiments failed to identify a critical role for TrioBP in early Xenopus development. For Cep4l, I found that overexpression of Cep4l induced primary neuron formation throughout the epidermis, preferentially inducing primary sensory neurons. This increase came at the expense of neighboring non-neuronal ciliated and ion-secreting cells, suggesting a role for Cep4l in neural boundary formation. Additionally, I have shown that Cep4l binds specifically to Cdc42 through its known Cdc42/Rac-interactive binding (CRIB) domain, and that this activation was necessary for Cep4l function.;Morpholino (MO) oligonucleotide based inhibition of Cep4l protein synthesis resulted in decreased primary sensory neurogenesis. Additionally, I have shown that Cdc42 itself is required for sensory neurogenesis. Furthermore, I find that Fgf8a, an isoform of Fgf8 previously known to regulate neuronal development, but not the Fgf8b isoform, regulates the association of Cep4l and Cdc42. Importantly, I further show that Cep4l and Cdc42 are required for the ability of Fgf8a to induce sensory neurons.;Overall, this work suggests a novel role for Cep4l and Cdc42 in the regulation of primary sensory neuronal fate downstream of a unique Fgf8 signaling pathway. I propose that binding of Fgf8a to its receptors activates Cdc42 and recruits Cep4l, which could serve as a scaffold for integrating additional signaling pathways involved in controlling sensory neuron fate.
机译：非洲爪蟾卵母细胞的植物皮层富含对于早期胚胎发育过程至关重要的几种mRNA，包括胚层规格和背腹轴形成。最近对其他植物定位的RNA进行的微阵列筛选确定了数百种新的富含皮质的转录本，这些转录本可能在早期发育中没有被发现。为了更好地阐明局部mRNA在早期发育中的功能，我表征了两种新的转录物TRIO和F-肌动蛋白结合蛋白（triobp）和Cdc42效应蛋白4类（cep41）的时空表达模式和发育功能。过表达和功能丧失实验未能确定TrioBP在非洲爪蟾早期发育中的关键作用。对于Cep41，我发现Cep41的过表达诱导了整个表皮的初级神经元形成，优先诱导初级感觉神经元。这种增加是以邻近的非神经纤毛和离子分泌细胞为代价的，表明Cep41在神经边界形成中的作用。另外，我已经证明Cep41通过其已知的Cdc42 / Rac相互作用结合（CRIB）结构域与Cdc42特异性结合，并且这种激活对于Cep41功能是必需的。原发性感觉神经发生。另外，我已经证明，Cdc42本身是感觉神经发生所必需的。此外，我发现Fgf8a（以前已知可调节神经元发育的Fgf8的同工型，而不是Fgf8b的同工型）可调节Cep41和Cdc42的结合。重要的是，我进一步表明，Cep41和Cdc42是Fgf8a诱导感觉神经元的能力所必需的。总的来说，这项工作表明Cep41和Cdc42在独特的Fgf8信号通路下游的初级感觉神经元命运的调节中具有新的作用。我建议Fgf8a与其受体的结合激活Cdc42并募集Cep4l，这可以用作整合涉及控制感觉神经元命运的其他信号传导途径的支架。

著录项

  • 作者

    Hulstrand, Alissa Marie.;

  • 作者单位

    The University of Iowa.;

  • 授予单位 The University of Iowa.;
  • 学科 Biology Genetics.;Health Sciences Human Development.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 133 p.
  • 总页数 133
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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