The University of Chicago, Department of Molecular Genetics and Cell Biology
Abstract: The importance of the extracellular matrix (ECM) in providing chemical and mechanical cues during development is widely appreciated. However, we know little about how cells produce ECMs, which must be tailored in not only composition, but also structure, to support each tissue’s needs. In the Drosophila ovary, the ECM that lines the epithelium surrounding the developing egg, the basement membrane (BM), is assembled into a fibril-filled sheet whose anisotropic mechanical properties guide tissue morphogenesis. Working in this epithelium, I found the subcellular secretion site of BM proteins is critically important in shaping the networks they form. Ex vivo live imaging revealed that two kinesin motors transport BM secretory vesicles along an unusual microtubule array polarized in two axes to spatially target secretion and promote assembly of fibrils. Without kinesin transport, BM networks form in the wrong location, where they interfere with cell movements during development, compromise the mechanical properties of the BM, and ultimately block egg production. A major roadblock to our understanding of how cells assemble ECM structures is the need to bridge two spatiotemporal scales: (1) the cell-scale, rapid processes of protein sorting, transport, and secretion; and (2) the tissue-scale process of ECM structure assembly, which can take days or weeks. Future work in this simple Drosophila model epithelium that rapidly produces a series of intricately structured ECMs will allow us to combine the power of Drosophila genetics with live imaging that spans the cell- and tissue-scale to gain new insights into the production of ECMs.
The department of Physiology & Biophysics acknowledges the Coast Salish peoples of this land, the land which touches the shared waters of all tribes and bands within the Suquamish, Tulalip and Muckleshoot nations. It is in this land where we work, teach, and learn.