IDENTIFICATION OF LHX TARGET GENES IN C ELEGANS

在秀丽隐杆线虫、果蝇和脊椎动物中的研究表明，LIM同源框基因（Lhx）在神经元分化中起着关键作用。该提案的总体目标是使用设计用于鉴定C中lim-6转录因子靶的遗传筛选来深入了解Lhx基因的功能。优雅实验设计利用了秀丽隐杆线虫的实验优势，包括遗传顺从性、其良好表征的神经系统和其完整的基因组序列。这些研究可能会剖析一个明确的GABA能神经元回路的功能所需的基因，以及阐明神经突发芽的过程。一个完整的阐明神经突发芽背后的分子事件有很大的希望提供一个了解Lhx基因是如何连接到这个过程。还值得注意的是，了解神经突发芽的分子基础是一个重要的目标，因为它发生在几种病理状态，如阿尔茨海默病，癫痫和其他神经退行性疾病。因此，这种方法很有可能揭示对理解神经分化至关重要的细节。

It is clear from work in Caenorhabditis elegans, Drosophila and vertebrates that LIM homeobox (Lhx) genes play pivotal roles in neuronal differentiation. The overall goal of this proposal is to gain insight into the function of Lhx genes using a genetic screen designed to identify targets of the lim-6 transcription factor in C. elegans. The experimental design makes use of the experimental advantages of C.elegans that include genetic amenability, its well-characterized nervous system, and its completed genome sequence. These studies are likely to dissect genes required for function of a defined GABAergic neuronal circuit as well as illuminate the process of neurite sprouting. A complete elucidation of the molecular events underlying neurite sprouting has great promise to provide an understanding of how Lhx genes are linked to this process. It is also worthwhile to note that understanding the molecular basis of neurite sprouting is an important goal given its occurrence in several pathological states such as Alzheimer's disease, epilepsy, and other neurodegenerative conditions. Thus, this approach is highly likely to uncover details of central importance to understanding neural differentiation.