Investigating germline stem cell abscission delay as a mechanism for stem cell coordination in the testis niche. Kari Lenhart, Steve DiNardo. Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA.
Tight regulation over stem cell proliferation and maintaining a consistent balance between self-renewal and differentiation are critical to ensure homeostasis in many organs. These properties of stem cells are regulated, at least in part, by the niche in which these cells reside. In the Drosophila testis, the niche contains three different cell types; the terminally differentiated hub cells that anchor the stem cells and provide self-renewing signals, along with somatic cyst stem cells (CySCs) and germline stem cells (GSCs). Both stem cell populations divide asymmetrically, with one daughter cell being retained at the hub and continuing to self-renew while the other is displaced from the niche and goes on to differentiate. Proper germ cell differentiation requires that the daughter of a GSC, the gonialblast (Gb), is associated with two somatic cyst cells, each derived from a flanking CySC; any disruptions of the interaction between cyst cells and the Gb lead to severe defects in differentiation. Thus, the production of progeny from CySCs and GSCs must be coordinated to achieve the proper 2:1 ratio of cyst cells to Gb. However, we found that CySCs and GSCs do not exhibit S-phase or M-phase synchrony, arguing against the simple model where cell cycle coordination achieves the necessary 2:1 ratio of cyst cells to Gb. We are instead focusing on a unique feature of GSC divisions as a potential means of stem cell coordination in the niche: the significantly delayed completion of cytokinesis during division of the GSC. Through a combination of genetic manipulations and live imaging, we are attempting to address whether the timing of GSC abscission is regulated by CySCs or cyst cells, as well as investigating how the block to cytokinesis is engaged within the GSCs, and what triggers its reinitiation.