Pax6 responsive genes and embryonic patterning

描述(由申请人提供)： 为了达到成熟大脑中发现的细胞类型的复杂性，胚胎中的生发区产生了不同类别的神经元。该项目旨在阐明这种生产序列是如何产生的，重点是对脑干小脑前神经元家族的产生至关重要的细胞命运指定事件。Dymecki实验室产生的重组酶命运映射系统提供了证据，支持小脑前神经元部分在菱形嘴唇中指定的模型。这项建议侧重于转录因子Pax6在小脑前系统规范中的作用。Pax6的缺失导致六个小脑前核团中的三个缺失。我假设小脑前神经元的特性部分是在菱形嘴唇中确定的，而在菱形嘴唇中表达的关键的“规范基因”是由Pax6调控的。这将在目标1中通过在全基因组水平上识别在菱形嘴唇中表达的Pax6靶标来进行检查。这些实验将与目标2中提出的那些实验相补充，后者使用Dymecki实验室建立的基于重组酶的命运映射工具来绘制Pax6基因缺失小鼠的菱形嘴唇组织发生图。

DESCRIPTION (provided by applicant): To achieve the complexity of cell types found in the mature brain, different classes of neurons are generated from germinal zones in the embryos. This project aims to elucidate how such production sequences arise, with emphasis on the cell fate specification events critical to the generation of a family of brainstem precerebellar neurons. The recombinase fate mapping system generated in the Dymecki lab provided evidence that supports the model that precerebellar neurons are specified, in part, in the rhombic lip. This proposal focuses on the role of the transcription factor Pax6 in the specification of the precerebellar system. Loss of Pax6 results in the absence of three of the six precerebellar nuclei. I hypothesize that the identities of the precerebellar neurons are specified, in part, in the rhombic lip and that critical "specification genes" expressed in the rhombic lip are regulated by Pax6. This will be examined in Aim 1 by identifying on a genome-wide level Pax6-targets expressed in the rhombic lip. These experiments will be complemented with those proposed in Aim 2 which use the established recombinase-based fate-mapping tools of the Dymecki lab to map rhombic lip histogenesis in Pax6-null mice.