Function of the Gli Genes in Sonic Hedgehog Signaling

描述（由申请人提供）：在这个更新项目中，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功能。具体来说，我们将研究Gli蛋白在Nestin祖细胞中在小鼠大脑生长和模式形成过程中的作用，重点关注它们在新皮层中的作用。我们还将研究Shh-Gli在神经干细胞中的功能，包括胚胎新皮层和出生后和成人侧脑室的室下区。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，特别强调新皮层，这是人类大脑功能的卓越结构。我们正在进行的关于祖细胞如何对施格利功能作出反应的研究将有助于理解大脑是如何形成的，这也将导致对许多精神缺陷的基础的理解。事实上，我们的研究结果可能会揭示患有前脑畸形（一种由SHH信号缺陷引起的疾病）的患者可能表现出的可能的精神缺陷。此外，sh - gli通路如何影响大脑前体的知识将有助于我们理解脑肿瘤是如何产生的，这是一个不同但相关的实验室项目所涵盖的研究领域。

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.