Unterschungen zur Bestimmung der Links-/Rechts-Asymmetrie regulierenden genetischen Netzwerke im Nervensystem des Nematoden Caenorhabditis elegans

神经系统的整体结构组织大多是双侧对称的。然而，从这种左/右（L/R）对称性的偏离以例如在其他对称结构中的不同基因表达模式的形式被观察到。In C.在elegans中，在化学感觉神经元ASEL和ASER中发现了不对称基因表达的一个有趣的例子，它们以左/右不对称的方式表达一组推定的化学感受器。化学感受器的不对称表达赋予了C.有能力区分不同化学感觉线索的秀丽线虫。我所在的实验室已经证明了几种转录因子可以控制这些化学感受器的不对称表达。本课题的目的是进一步剖析基因调控网络，并描述在C.优雅我将研究如何以前确定的转录因子和那些将从我的生物化学研究发现的行为建立ASEL/R不对称的分子基础。在全基因组大规模的方法，我将发现新的靶基因的不对称调节因子的ChIP检测结合芯片分析。由于基因转录的表观遗传调控对于决定细胞命运的规范至关重要，我也将研究染色质修饰在建立ASE L/R不对称性中的作用。神经不对称控制机制的识别将提供对一般大脑模式的主要见解。

The overall structural organization of the nervous system is mostly bilaterally symmetric. However, deviations from this left/right (L/R) symmetry are observed in the form of, for example, different patterns of gene expression in otherwise symmetrical structures. In C. elegans, an interesting example of asymmetric gene expression is found in the chemosensory neurons ASEL and ASER, which express a set of putative chemoreceptors in a left/right asymmetric manner. Asymmetric expression of chemoreceptors endows C. elegans with the ability to discriminate between distinct chemosensory cues. Several transcription factors have been shown by my host laboratory to control asymmetric expression of these chemoreceptors. The aim of my project is to further dissect the gene regulatory networks and describe the motifs of regulation that control the L/R asymmetries observed in the ASE neurons of C. elegans. I will investigate the molecular basics of how the previously identified transcription factors and those that will be discovered from my biochemical investigations act to establish ASEL/R asymmetry. In a genome wide large scale approach, I will discover new target genes of the asymmetry regulating factors by ChIP assays combined with microarray analysis. Since epigenetic regulation of gene transcription is of crucial importance for determining cell fate specification I will also investigate the role of chromatin modification in establishing ASE L/R asymmetry. The identification of neural asymmetry-controlling mechanisms will provide major insights into brain patterning in general.