PgmNr D1211: Investigating the role of intracellular pH in epithelial stem cell differentiation.

Authors:
M. Benitez; B. Ulmschneider; B. Grillo-Hill; D. Barber; T. Nystul


Institutes
University of California-San Francisco, San Francisco, CA.


Keyword: follicle stem cell

Abstract:

Transitions in the fate or morphological state of epithelial cells are central to metazoan development, homeostasis, and tissue repair. We are using the follicle stem cell (FSC) lineage in the Drosophila ovary as a model to investigate the potential role of intracellular pH (pHi) in cellular differentiation in an adult stem cell lineage. We found that pHi increases naturally during follicle cell differentiation and that blocking this increase interferes with differentiation toward the polar/stalk cell fate. To investigate how pHi is controlled during follicle cell differentiation, we performed an RNAi screen through a collection of 20 genes that are predicted to regulate pHi. Our preliminary studies identified three genes from this collection that are required for follicle cell differentiation. We found that RNAi knockdown of CG8177, CG13384 and CG32081 prevents proper FSC development, leading to abnormal and ectopic polar/stalk cell formation. We are currently investigating how the knockdown of these genes affects follicle cell pHi. Lastly, we are investigating whether changes in pHi promote follicle cell differentiation by inhibiting Hedgehog pathway activity. Collectively, these studies will provide insight into a novel form of regulation of cellular differentiation in an epithelial stem cell lineage.