Hippo signaling in mouse liver development and regeneration

描述(申请人提供)：河马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。在哺乳动物系统中对河马信号通路的研究直到最近才真正开始，仍然有许多悬而未决的问题。在拟议的研究中，我们将重点关注与发育中的河马信号通路和组织动态平衡相关的三个领域，重点是以小鼠肝脏为模型系统。首先，将探讨河马信号在调节胚胎干细胞和祖细胞增殖、分化和自我更新中的作用。其次，我们将确定河马信号在调节成年肝干细胞和祖细胞增殖、分化和自我更新中的细胞自主和非自主作用。最后，我们将利用我们最近完成的基于体内转座子的突变筛查来确定新的河马途径组件和与河马信号整合的途径，以调节肝细胞的生长。

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.