Function of the Gli Genes in Sonic Hedgehog Signaling

Gli 基因在 Sonic Hedgehog 信号转导中的功能

• 批准号: 7082402
• 负责人: Ariel Ruiz i Altaba
• 金额: $ 34.94万
• 依托单位: UNIVERSITY OF GENEVA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-20 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7082402
• 关键词: age difference; athymic mouse; biological signal transduction; cerebral ventricles; congenital brain disorder; developmental genetics; developmental neurobiology; embryo /fetus; gene expression; genetically modified animals; infant animal; laboratory mouse; mature animal; neocortex; nerve stem cell; neurogenesis; neurons; protein structure function; transcription factor

DESCRIPTION (provided by applicant): In this renewal project we propose to continue our research on the functions of the Sonic hedgehog (Shh)-Gli pathway in neural development during embryonic, perinatal and adult stages using the mouse as an experimental model. Specifically, we will study the role of Gli protein function in Nestin progenitors during mouse brain growth and patterning, focusing on their role in the neocortex. We will also investigate Shh-Gli function in neural stem cells, from both the embryonic neocortex and the postnatal and adult subventricular zone of the lateral ventricle. The results of our proposed research will help in understanding how this important signaling pathway regulates the growth and patterning of the brain, with special emphasis placed on the neocortex, a preeminent structure in human brain function. Our ongoing research on how progenitor cells respond to Shh-Gli function will help in understanding how the brain is formed, which will also lead to an understanding of the bases of a number of mental deficits. Indeed, our findings will likely shed light into the possible mental deficits that patients with viable forms of holoprosencephaly (a disease that can arise from defective SHH signaling) may display. In addition, the knowledge of how the SHH-GLI pathway affects brain precursors will help our understanding of how brain tumors arise, an area of research covered under a different, yet related, project in the laboratory.

描述(申请人提供)：在本次更新项目中，我们建议以小鼠为实验模型，继续研究Sonic hedgehog(Shh)-Gli通路在胚胎、围产期和成年期神经发育中的作用。具体地说，我们将研究Gli蛋白在巢蛋白前体细胞在小鼠大脑生长和构图过程中的作用，重点是它们在新皮质中的作用。我们还将研究Shh-Gli在神经干细胞中的功能，包括来自胚胎新皮质以及出生后和成人侧脑室下区的神经干细胞。我们提出的研究结果将有助于理解这一重要的信号通路如何调节大脑的生长和模式，特别是新皮质，这是人类大脑功能中的一个卓越结构。我们正在进行的关于祖细胞如何对Shh-Gli功能做出反应的研究将有助于理解大脑是如何形成的，这也将导致对一些精神缺陷的基础的理解。事实上，我们的发现可能会揭示有存活形式的全前脑畸形(一种可能由SHH信号缺陷引起的疾病)患者可能表现出的精神缺陷。此外，了解SHH-GLI途径如何影响大脑前体将有助于我们理解脑瘤是如何发生的，这是实验室另一个不同但相关的项目所涵盖的研究领域。