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.
The BMP signaling pathway is a major regulator of cell proliferation, fate and differentiation across organisms. In addition, BMP pathway dysfunction is associated with cancer and other human disorders. Pathway components are highly conserved across the animal kingdom and homologues have been identified from nematodes to humans. Understanding mechanisms that influence pathway activity has broad implications for areas of stem cell research, developmental biology, and the study of human diseases.
|Dolezal, Darin; Liu, Zhiyan; Zhou, Qingxiang et al. (2015) Fly LMBR1/LIMR-type protein Lilipod promotes germ-line stem cell self-renewal by enhancing BMP signaling. Proc Natl Acad Sci U S A 112:13928-33|