Left/right asymmetric neuronal cell fate specification

描述(由申请人提供)： 神经系统偏侧性是发育神经生物学中最基本但也是研究最少的现象之一。神经系统在结构水平上通常是两侧对称的，但表现出显著程度的功能性左/右(L/R)不对称。大脑的左右两边是如何变得不同的，从机械上讲还没有被理解。我们建议在这里研究线虫中神经元偏侧性的一个例子，这是一个特别适合研究这个问题的系统，因为神经元偏侧性可以在单个细胞水平上观察到，并且可以从基因上进行观察。 使用突变筛选方法进行解剖。我们将从基因上分析L/R两个神经元规范程序的差异执行情况，这两个程序来自两个双边对称的原始细胞，ABp1Papp和ABprPapp。每个原始细胞分裂几次，产生一组不成对的单侧神经元。我们将分离这些L/R不对称分化程序被打乱的突变体。这些研究可能揭示神经元发育的基本原理，并可能揭示神经系统中产生L/R不对称的难以捉摸的机制。

DESCRIPTION (provided by applicant): Nervous system laterality represents one of the most fundamental, yet also least studied phenomena in developmental neurobiology. Nervous systems are generally bilaterally symmetric on an architectural level, yet display significant degrees of functional left/right (L/R) asymmetry. How the left and right side of a brain are made to become different from one another is mechanistically not understood. We propose here to study one of the examples of neuronal laterality in the nematode C.elegans, a system particularly well amenable to study this problem since neuronal laterality can be observed on a single cell level and can be genetically dissected using mutant screening approaches. We will genetically analyze the L/R differential execution of two neuronal specification programs that derive from two bilaterally symmetric blast cells, ABp1papp and ABprpapp. Each blast cell divides several times to produce a distinct set of unpaired, unilateral neurons. We will isolate mutants in which these L/R asymmetric differentiation programs are disrupted. These studies may reveal fundamental principles of neuronal development and may shed light onto the elusive mechanisms of generating L/R asymmetry in the nervous system.