BMP signaling and cell fate in the embryonic endoderm

描述(由申请人提供) 这项提议的目标是了解细胞外信号分子如何 指导胚胎发育过程中特化细胞类型的形成。 骨形态发生蛋白(BMPs)在肝脏早期发育中的作用 使用小鼠组织外植体培养实验来确定如何 内胚层中未固定的细胞被引导成为肝细胞。角色 BMP在其他内胚层器官细胞类型的规范中的作用，包括 胰腺和甲状腺，将进行研究，以确定该信号分子 致力于肝脏发育或在内胚层器官中扮演一般角色 队形。骨形态发生蛋白途径和成纤维细胞的信号转导成分 生长因子(FGFs)途径，另一个促进肝脏发育的信号， 将被监控以确定这些信号之一是否允许目标小区 处理另一个信号。被激活的转录因子的作用 将对BMP进行检查，以了解它们如何与内胚层因子合作 进行骨形态发生蛋白依赖的基因调控。该项目旨在提供一种 前体内胚层细胞如何处理细胞外的多角度视角 BMP发出信号，并致力于肝脏的命运。关于天然细胞的知识 分化将促进操纵细胞分化的目标 出于医疗目的。

DESCRIPTION (provided by applicant) The goal of this proposal is to learn how extracellular signaling molecules direct the formation of specialized cell types during embryonic development. The role of bone morphogenetic proteins (BMPs) in early liver development will be studied using a mouse tissue explant culture assay to determine how uncommitted cells in the endoderm are directed to become liver cells. The role of BMP in the specification of other endoderm organ cell types, including pancreas and thyroid, will be studied to determine if this signaling molecule is dedicated to liver development or plays a general role in endoderm organ formation. Signal transduction components of the BMP pathway and the fibroblast growth factors (FGFs) pathway, another signal that promotes liver development, will be monitored to determine if one of these signals permits a target cell to process the other signal. The role of transcription factors that are activated by BMPs will be examined to learn how they cooperate with endoderm factors to carry out BMP-dependent gene regulation. This project is designed to provide a multifaceted view of how a precursor endoderm cell processes an extracellular BMP signal and is committed to a liver fate. Knowledge of natural cell differentiation will promote the goal of manipulating cell differentiation for medical purposes.