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Regulation of Neurogenesis by Jagged1 in the Embryonic SVZ

Jagged1 在胚胎 SVZ 中对神经发生的调节

基本信息

批准号：
8444257
负责人：
Christopher Alexander Blackwood
金额：
$ 0.58万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-16 至 2013-07-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444257
关键词：
Affect Antibodies Automobile Driving B-Lymphocytes Binding Sites Brain Bromodeoxyuridine Cell division Cells Conflict (Psychology)Control Animal Drops Embryo Glial Fibrillary Acidic Protein Goals Health Hippocampus (Brain)Immunohistochemistry In Vitro Ischemia Label Ligands Lithium Chloride Luciferases Mediating Memory NCAM1 gene Neurons Notch Signaling Pathway Olfactory Learning Phenotype Play Process Production Proliferating Proliferating Cell Nuclear Antigen Quercetin Regulation Relative (related person)Reporting Role Signal Transduction Stem cells Stream Stroke Structure of thyroid parafollicular cell System Testing Up-Regulation cancer cell cell type inhibitor/antagonist jagged1 protein mutant nerve stem cell neuroblast neurogenesis notch protein olfactory bulb progenitor promoter public health relevance subventricular zone

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to investigate the role of Jagged1 during late embryonic neurogenesis in the subventricular zone (SVZ) of the olfactory system. Prior studies have shown that loss of Jagged1 leads to reduced cell division within the SVZ. However, what cell-types are affected within the SVZ to produce this phenotype is still unknown. In the SVZ, neural stem cells give rise to transit amplifying cells, which in turn produce neuroblast precursors. I hypothesize that Jagged1 is required for one or both of these transitions during neurogenesis. I will use Jagged1 mutants and immunohistochemical approaches to determine what cell types are affected during neurogenesis. Jagged1 is known to regulate cells division in the SVZ. However, what mechanisms control Jagged1 activation and expression? It has been shown that Jagged1 is activated by wnt signaling in cancer cells. Wnt is also known to regulate neurogenesis in the brain, but how this process occurs is still poorly understood. I hypothesize that wnt regulates neurogenesis by controlling Jagged1 expression in the SVZ. I will use SVZ-derived neurospheres and pharmacological approaches to determine if Jagged1 mediates wnt regulation of neurogenesis.

描述（由申请人提供）：本提案的目的是研究Jagged 1在嗅觉系统脑室下区（SVZ）胚胎晚期神经发生过程中的作用。先前的研究表明，Jagged1的缺失导致SVZ内细胞分裂减少。然而，在SVZ内哪些细胞类型受到影响而产生这种表型仍然是未知的。在SVZ中，神经干细胞产生运输放大细胞，其反过来产生神经母细胞前体。我推测，锯齿状蛋白1是必要的一个或两个在神经发生过程中的这些过渡。我将使用Jagged1突变体和免疫组织化学方法来确定在神经发生过程中哪些细胞类型受到影响。已知Jagged 1可以调节SVZ中的细胞分裂。然而，什么机制控制Jagged1激活和表达？研究表明，Jagged1在癌细胞中被wnt信号激活。Wnt也被认为可以调节大脑中的神经发生，但是这个过程是如何发生的仍然知之甚少。我推测wnt通过控制SVZ中Jagged1的表达来调节神经发生。我将使用SVZ衍生的神经球和药理学方法来确定Jagged1是否介导Wnt对神经发生的调节。