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两侧对称的。然而，这种左/右（L/R）对称的偏差被观察到，例如，在其他对称结构中，不同的基因表达模式。在秀丽隐杆线虫中，在化学感觉神经元ASEL和ASER中发现了一个有趣的不对称基因表达的例子，它们以左/右不对称的方式表达一组假定的化学感受器。化学感受器的不对称表达赋予秀丽隐杆线虫区分不同化学感觉信号的能力。我的宿主实验室已经证明了几种转录因子可以控制这些化学受体的不对称表达。我的项目目的是进一步剖析基因调控网络，并描述在秀丽隐杆线虫的ASE神经元中观察到的控制L/R不对称的调控基序。我将研究先前确定的转录因子和那些将从我的生化调查中发现的转录因子如何建立ASEL/R不对称的分子基础。在全基因组大范围的方法中，我将通过ChIP检测结合微阵列分析发现新的不对称调节因子靶基因。由于基因转录的表观遗传调控对于决定细胞命运规范至关重要，我还将研究染色质修饰在建立ASE L/R不对称中的作用。神经不对称控制机制的识别将为一般的大脑模式提供重要的见解。

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.