View Program - 63rd Annual Drosophila Research Conference

So-called ‘organizer cells’ help other cells develop through directing cell fate specification, stem cell maintenance, and even cell migration. Often these various organizer cell functions are due to production of secreted, diffusible signals that initiate specific responses in neighboring cells. One such organizer is the polar cells that form at the anterior and posterior poles of egg chambers, the functional units of the developing ovary. Polar cells are initially produced in excess. Regulated apoptosis eliminates these ‘supernumerary’ polar cells to produce the ‘mature’ polar cell pairs. Later in oogenesis, the anterior polar cell pair secretes the cytokine Unpaired to activate JAK/STAT signaling in adjacent follicle cells, which become migratory border cells. If excess polar cells survive, too many border cells are recruited, whereas if one or both mature polar cells die, too few border cells form, either of which inhibits successful migration. Thus, survival and maintenance of the mature polar cells must be tightly regulated so only two polar cells survive, yet the mechanisms regulating this are unclear. Here we show that the small GTPase Rap1 controls border cell cluster size by promoting survival of the mature polar cells. We found that egg chambers deficient for Rap1 form border cell clusters with fewer cells than normal. At least 20% of border cell clusters were missing at least one polar cell in addition to fewer border cells. Loss of Rap1 did not alter polar cell specification or the timely elimination of supernumerary polar cells during early oogenesis. Nor did Rap1 regulate activation of STAT in the follicle cells that will form the border cell cluster. Instead, during mid-oogenesis, Rap1 maintained the viability of anterior follicle cells including the mature polar cells. Without proper Rap1 activity, one or both anterior polar cells underwent apoptosis resulting in smaller border cell clusters. Notably, Rap1-deficient border cell cluster size was rescued by blocking cell death using the apoptosis inhibitor p35. These data together show that Rap1 regulates cell survival through blocking apoptosis, resulting in clusters with the optimal number of border cells. Remarkably, Rap1-deficient polar cell shape was drastically altered, potentially contributing to polar cell death. Thus, Rap1 is a new regulator of organizer cell viability that promotes polar cell survival and morphogenesis to build the migratory border cell collective.

The small GTPase Rap1 promotes polar cell survival and morphogenesis to form the migratory border cell cluster