A Role for Prolyl-4-Hydroxylase Alpha in Cell Migration During Oogenesis. Jinal S. Sheth, Michelle Starz-Gaiano. Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD.

   During animal development, some cells are required to migrate at a precise time to fulfill their destiny. One such example is guided migration of border cells during oogenesis. Border cells are a group of 6-10 follicular epithelial cells that delaminate at the anterior of the egg chamber and migrate as a compact cluster posteriorly towards the oocyte. Developmental specification of border cells and their subsequent migration is induced by activation of the Janus Kinase and Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway. We have identified a gene, prolyl-4-hydroxylase alpha (PH4alphaEFB), expressed in follicle cells at the time of border cell movements, that may be an important mediator of signaling. To characterize the function of the PH4alphaEFB gene better, we studied several putative loss of function mutations with transposable elements inserted at this locus. We determined the strongest mutant allele of PH4alphaEFB through genetic and molecular analysis and comparison with a deficiency. Loss of function mutations all affected oocyte growth, and some alleles also disrupted border cell migration. It has been known that PH4alphaEFB family members can regulate Collagen IV, a component of extracellular matrix. In addition, collagen is also well known for a role in shaping the elongated egg chamber, but its role in border cell movement is less clear. Other experiments suggest PH4alpha may interact with the receptor that activates STAT family. We are currently investigating a link between PH4alphaEFB and regulation of Collagen IV and STAT activation. The success of this project will contribute to a better understanding of border cell migration and may provide insight into cell movement more generally.