Diversity Along the Left/Right Axis in Nervous System

双侧对称性是神经系统发育史上的一个共同特征。 形态对称性与许多不同神经系统的偏侧化形成对比。 功能，可能是由于个别细胞类型沿途采用不同的命运和功能所致 左/右(L/R)轴。沿L/R轴创造细胞多样性的分子机制 然而，人们对神经系统知之甚少。线虫的神经系统 秀丽线虫显示了几个偏侧化的例子，包括L/R不对称 由两个ASE味觉感受器神经元显示，ASE左侧(ASEL)和ASE右侧(ASER)。而当 根据所有已知的形态标准，这两个神经元显示出不同的化学感觉能力，这与三个假定的化学受体L/R的不对称表达有关。我们的目的是了解L/R不对称细胞命运是如何在ASEL和ASER神经元中创造的。我们假设L/R不对称是由一个未知分子性质的信号引起的。我们建议使用激光消融来确定信号的细胞来源(目标1)，并建议通过表征我们从L/R不对称缺陷的遗传筛查中分离的突变来了解信号的分子性质(目标2)。我们之前的遗传分析已经揭示了一系列基因调控因子(包括同源盒基因和miRNAs)，它们作用于Asel和ASER，使它们各自的命运多样化。未来的遗传学研究将确定这些基因调控因子的不对称活性是如何被触发的。我们的研究可能会为神经系统中细胞多样性的创造提供新的见解。

Bilateral symmetry is a common feature of nervous system anatomy across phylogeny. Morphological symmetry is contrasted by the lateralization of many different nervous system functions, likely caused by individual cell types adopting different fates and functions along the left/right (L/R) axis. The molecular mechanisms of creating cellular diversity along the L/R axis in the nervous system are, however, poorly understood. The nervous system of the nematode Caenorhabditis elegans displays several examples of lateralization, including the L/R asymmetry displayed by the two ASE taste receptor neurons, ASE left (ASEL) and ASE right (ASER). While bilaterally symmetric in regard to all known morphological criteria, these two neurons display distinct chemosensory capacities which correlate with the L/R asymmetric expression of three putative chemoreceptors. We aim to understand how L/R asymmetric cell fate is created in the ASEL and ASER neurons. We hypothesize that L/R asymmetry is induced by a signal of unknown molecular nature. We propose to use laser ablation to identify the cellular source of the signal (Aim #1) and we propose to understand the molecular nature of the signal by characterizing mutants which we isolated from a genetic screen for L/R asymmetry defects (Aim #2). Our previous genetic analysis has already revealed a cascade of gene regulatory factors (including homeobox genes and miRNAs) that act in ASEL and ASER to diversify their respective fates. Future genetic studies will determine how the asymmetric activity of these gene regulatory factors is triggered. Our studies may provide novel insights into the creation of cellular diversity in the nervous system.