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Hippo signaling in mouse liver development and regeneration

小鼠肝脏发育和再生中的 Hippo 信号传导

基本信息

批准号：
8729727
负责人：
Randy L. Johnson
金额：
$ 23.7万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-18 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8729727
关键词：
Adult Appearance Area Biliary Biological Models Cell Count Cell Cycle Cell Differentiation process Cell Lineage Cell Proliferation Cells Development Disease Drosophila genus Drug Metabolic Detoxication Embryo Epithelial Epithelial Cells Genes Genetic Programming Growth Hepatocyte Homeostasis Injury Liver Liver Regeneration Liver Stem Cell Maintenance Mammals Mediating Metabolism Molecular Mus Mutagenesis Mutate Natural regeneration Organ Pathway interactions Phosphotransferases Play Population Process Production Property Regulation Reporting Research Role Signal Pathway Signal Transduction Sleeping Beauty Stem cells System Testing Therapeutic Tissues To specify Tumor Suppressor Proteins base cell growth cell type cofactor design in vivo injured insight liver cell proliferation liver function liver repair mutant novel oval cell prevent progenitor public health relevance reconstitution repaired response self-renewal stem stem cell population tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): The Hippo signaling pathway is an emerging growth control and tumor suppressor pathway that is conserved between Drosophila and mammals. Study of the Hippo signaling pathway in mammalian systems has only recently begun in earnest and many outstanding questions remain. In the proposed research we will focus on three areas pertinent to Hippo pathway signaling in development and tissue homeostasis, focusing on the mouse liver as a model system. First, the role of Hippo signaling in regulation of embryonic stem and progenitor proliferation, differentiation, and self-renewal will be explored. Second, we will define cell autonomous and cell non-autonomous roles for Hippo signaling in regulation of adult liver stem and progenitor cell proliferation, differentiation, and self-renewal. Finally, we will tke advantage of our recently completed in vivo transposon-based mutatagenesis screen to identify novel Hippo pathway components and pathways that integrate with Hippo signaling to regulate liver cell growth.

描述（由申请人提供）：Hippo信号通路是一种新兴的生长控制和肿瘤抑制通路，在果蝇和哺乳动物之间保守。哺乳动物系统中河马信号通路的研究直到最近才真正开始，许多悬而未决的问题仍然存在。在拟议的研究中，我们将重点关注Hippo通路信号在发育和组织稳态中的三个相关领域，重点关注小鼠肝脏作为模型系统。首先，将探讨Hippo信号在胚胎干细胞和祖细胞增殖、分化和自我更新调控中的作用。其次，我们将定义Hippo信号在成人肝干细胞和祖细胞增殖、分化和自我更新调控中的细胞自主和细胞非自主作用。最后，我们将利用我们最近完成的基于转座的体内突变筛选来鉴定新的Hippo通路成分和与Hippo信号整合以调节肝细胞生长的通路。