A niche-associated polarity ensures the asymmetric self-renewing divisions of germline stem cells of the Drosophila ovary

Adult stem cells divide asymmetrically to balance self-renewal versus differentiation. Many adult stem cells reside in a microenvironment, called a niche, which is necessary for stem cell maintenance. The female germline stem cells (GSCs) of the Drosophila ovary are an excellent system to study niche-stem cell interactions. Previous studies have shown that the somatic niche composed of Cap cells (CpC) anchors the GSCs through Adherens Junctions (AJs) and secretes Bone Morphogenesis Proteins (BMPs) to maintain the GSCs in the niche as undifferentiated, mitotically-active cells. GSCs normally divide perpendicular to the CpC-GSC interface so that one daughter cell remains in the niche as a GSC, while the other daughter cell is born outside the niche and begins the process of differentiation.This thesis demonstrates that a niche-associated polarity complex, composed of the Par-3 homolog Bazooka (Baz), the Rac GEF Still life (Sif) and the small GTPase Rac, controls both GSC centrosome orientation and promotes BMP signaling in the GSC, thereby coupling the control of the GSC division plane with an asymmetric response to the BMP maintenance signal. However, additional activities are redundant with each of the functions of the Baz complex. In particular, GSCs with misoriented centrosomes are arrested at prometaphase by a novel cell cycle checkpoint. Therefore, the somatic CpC niche controls GSC maintenance extrinsically through BMP signaling, and intrinsically through GSC polarization by the Baz/Sif/Rac complex.These data raised the question of how the Baz/Sif/Rac complex is established and maintained at the niche-GSC interface. Additional experiments demonstrated that two other components of the Par gene network, Par-1 and Par-5, are necessary to restrict Par-3/Baz localization to the niche-GSC interface, establishing a novel use of this conserved genetic network to polarize the GSCs. Additionally, AJs both stabilize Baz and promote BMP signaling in the GSCs, suggesting that AJs may be the cue that initially polarizes the GSC during larval development.Lastly, preliminary data indicate that Par-1 and the mitotic kinase Aurora A are both downstream components of the centrosome orientation checkpoint, thereby linking genes involved in cellular polarity with fundamental components of the cell cycle machinery. Together, these data begin to provide insights into the complexities of the genetic architecture necessary to ensure a robust pattern of asymmetric self-renewing divisions within a niche-resident adult stem cell.