DPP/ BMP signaling in Stem Cells and Development

描述(申请人提供)：果蝇雌性生殖系干细胞(GSCs)是所有生物体中研究最好的干细胞模型之一，允许在体内进行单细胞分辨率分析。我们的实验室已经发现，一种没有特征但高度保守的跨膜蛋白对于果蝇卵巢中生殖系干细胞的自我更新是必要的和充分的。有趣的是，在BMP信号的背景下，这个因子似乎起到了内吞受体的作用。这一建议研究了它如何在分子水平上发挥作用，特别是它是作为Mad磷酸化所需的BMP途径的更核心的组成部分，还是作为已知调控途径或另一个更一般的生物过程的核心级联的调节器。我们也开始表征一个假定的配体。由于BMP途径对后生动物的发育和成体动态平衡具有普遍的重要性，而且途径成分在进化上是保守的，在动物中就像线虫和人类一样，因此拟议的工作对干细胞研究、发育生物学和人类疾病的研究具有广泛的意义。

DESCRIPTION (provided by applicant): The Drosophila female germline stem cells (GSCs) is among the best-studied stem cell models in any organism permitting analysis at single cell resolution in vivo. Our laboratory has discovered that an uncharacterized, but highly conserved, transmembrane protein is necessary and sufficient for germline stem cell self-renewal in the fly ovary. Interestingly, this factor appears to function as an endocytic receptor in the context of BMP signaling. This proposal investigates how it functions at the molecular level and particularly whether it serves as a more central component of the BMP pathway required for Mad phosphorylation, or as a modulator of the core cascade through known regulatory pathways or another, more general biological process. We also begin the characterization of a putative ligand. Since the BMP pathway is universally important for development and adult homeostasis of metazoa, and pathway components are evolutionarily conserved in animals as different as nematodes and humans, the proposed work has broad implications for areas of stem cell research, developmental biology, and the study of human diseases.