Molecular genetic analysis of hindlimb development in zebrafish

斑马鱼后肢发育的分子遗传学分析

• 批准号: 263801744
• 负责人: Professor Dr. Gerrit Begemann
• 金额: --
• 依托单位: Lehrstuhl für Tierphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/263801744?language=en
• 关键词: Molecular; genetic; analysis; hindlimb; development

Despite the complexity of human congenital limb formations and their relative abundance, the molecular mechanisms underlying and specific to pelvic fin/hindlimb formation in the zebrafish have largely been unexplored. We propose to unravel the molecular regulation of zebrafish pelvic fin/hindlimb formation using various genetic approaches. To this end, (I) we will clone and examine a novel mutant with severe defects in the formation of pelvic fins and associated endoskeleton, (II) we will test the hypothesis that RA signaling is required for pelvic fin initiation and will examine an unexpected involvement in patterning the pelvic fin endoskeleton, and (III) we will develop transgenic tools that allow us to manipulate RA signaling, and ultimately any signaling pathway, in developing pelvic fins in a tissue-specific manner and at any given time. Together, our work should provide new and significant insights into the regulation of vertebrate hindlimb development. Our findings should be relevant for a better understanding of the underlying mechanisms leading to congenital deformities of tetrapod limbs.

尽管人类先天性肢体形成的复杂性和相对丰富，但斑马鱼腹鳍/后肢形成的分子机制基本上尚未探索。我们建议解开斑马鱼腹鳍/后肢形成的分子调控使用各种遗传方法。为此，（I）我们将克隆并检查一种在腹鳍和相关内骨骼形成中具有严重缺陷的新突变体，（II）我们将测试RA信号传导是腹鳍起始所需的假设，并将检查在腹鳍内骨骼图案化中意外参与的假设，以及（III）我们将开发允许我们操纵RA信号传导的转基因工具，以及最终的任何信号通路，以组织特异性的方式和在任何给定的时间发育腹鳍。总之，我们的工作将为脊椎动物后肢发育的调控提供新的重要见解。我们的研究结果应该是相关的更好地理解的潜在机制，导致先天性畸形的四足动物的四肢。