Hippo signaling in mouse liver development and regeneration

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。

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.