同源异型域转录因子VAB-15对线虫神经前体细胞命运的调控

项目名称： 同源异型域转录因子VAB-15对线虫神经前体细胞命运的调控

项目编号： No.31471371

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘晓

作者单位： 清华大学

项目金额： 80万元

中文摘要： 神经前体细胞具有从上皮类前体细胞分化而获得神经潜能的普遍性,而不同神经前体细胞可以有生成不同神经类型的特异性，这是神经系统发育和维持的基础。因此研究神经前体细胞命运决定的分子机制对认识神经系统的形成有重要意义。线虫神经发育生物学研究已经鉴定出若干控制神经前体细胞获得神经潜能的原神经基因。这些原神经基因主要控制感觉神经前体细胞的命运决定，且多为bHLH家族转录因子。然而其它神经前体细胞的命运决定机制还尚待研究。我们的前期工作发现高度保守的同源异型结构域转录因子VAB-15在胚胎后期特异表达在不同类型的神经前体细胞中，并影响其神经潜能。本课题将结合单细胞精度影像分析、组织特异转录组技术和遗传分析方法，揭示VAB-15在神经前体细胞命运决定中的作用，鉴定并研究其调控回路。本课题着重揭示和比较VAB-15在感觉神经前体细胞和运动神经前体细胞中的调控回路，探讨调控神经潜能的分子机制的普遍性和特异性。

中文关键词： 神经前体细胞；细胞谱系；细胞命运；转录因子；秀丽隐杆线虫

英文摘要： Nearly all neuroblasts gain neuropotency by differentiation from epithelial-like precursors. On the other hand, various neuroblasts can generate different neural types. The universaity and specificity are basis of development and homeostasis of neural systems. So investigating molecular mechanisms underlying neuroblast cell fate is important to understand neurogenesis. Studies of neurogenesis in C. elegans have identified several genes involved in neuropotency of neuroblasts. Most of these proneural genes major in controlling cell fates of sensory neuronal precursors, and most of them are bHLH transcription factors. However, molecular mechanisms of cell fate determination of other neuronal precursors remain elusive. Our preliminary investigation discovered that VAB-15, a highly conserved HD transcription factor, was expressed in multiple embryonic neuroblasts and controlled their neuropotentcy. Combining imaging analysis at the resolution of single cell, tissue-specific gene expression profiling and genetic assays, this project aims to investigate the role of VAB-15 in cell fate determination of neuroblasts, identify and investigate its downstream target genes and upstream regulators. Especially, this project will reveal and compare gene regulation circuits in precursors of sensory neurons and those in motor ones to address universality and specificity of neuropotency.

英文关键词： neuroblast;cell lineage;cell fate;transcription factor;Caenorhabditis eleans