Pax6 responsive genes and embryonic patterning

Pax6 响应基因和胚胎模式

• 批准号: 6938741
• 负责人: REBECCA L LANDSBERG
• 金额: $ 4.83万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938741
• 关键词: brain morphology; cell differentiation; developmental genetics; embryogenesis; gene expression; genetically modified animals; laboratory mouse; microarray technology; neurogenesis; neurogenetics; postdoctoral investigator; rhombencephalon; transcription factor

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.

描述（由申请人提供）： 为了实现成熟大脑中发现的细胞类型的复杂性，不同类别的神经元从胚胎中的生发区产生。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规范事件。Dymecki实验室产生的重组酶命运映射系统提供了支持小脑前神经元部分在菱形唇中指定的模型的证据。这项建议的重点是转录因子Pax6在小脑前系统的规范中的作用。Pax6的缺失导致六个小脑前核中的三个缺失。我推测，小脑前神经元的身份是指定的，在部分，在菱形唇和关键的“规格基因”在菱形唇的调节Pax6。这将在目的1中通过在全基因组水平上鉴定菱形唇中表达的Pax6靶来检查。这些实验将与目标2中提出的那些实验进行补充，目标2使用Dymecki实验室建立的基于重组酶的命运作图工具来绘制Pax6缺失小鼠中的菱形唇组织发生。