DPP/ BMP signaling in Stem Cells and Development

描述（由申请方提供）：果蝇雌性生殖系干细胞（GSC）是允许在体内进行单细胞分辨率分析的任何生物体中研究最好的干细胞模型之一。我们的实验室已经发现，一个未知的，但高度保守的，跨膜蛋白是必要的和足够的生殖干细胞自我更新的苍蝇卵巢。有趣的是，该因子似乎在BMP信号传导的背景下作为内吞受体起作用。该提案研究了它如何在分子水平上发挥作用，特别是它是否作为Mad磷酸化所需的BMP途径的更核心的组分，或者作为通过已知的调节途径或另一种更一般的生物过程的核心级联的调节剂。我们也开始表征一个假定的配体。由于BMP通路对后生动物的发育和成体体内平衡普遍重要，并且通路组分在动物中进化上保守，如线虫和人类，所提出的工作对干细胞研究，发育生物学和人类疾病的研究领域具有广泛的影响。

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.