Switching On/Off the Hh signalling Pathway Determines Niche Cell Fates of Ovarian Germline Stem Cells
Authors: Yu-Ting Wang 1,2; Chun-Ming Lai 3; Hwei-Jan Hsu 1,2
Affiliations: 1) Academia Sinica, Taipei City, Taiwan; 2) National Defense Medical Center, Taipei City, Taiwan; 3) Louisiana Cancer Research Center, Tulane University, LA, USA
Keywords: b. germline stem cell; a. Hedgehog
The balance between stem cell renewal and differentiation is critical for tissue homeostasis, and that is largely regulated by stem cell microenvironments, or niches, formed by specific groups of cells. The stem cell maintenance niche recruits and maintains stem cell pool, while the stem cell differentiation niche promotes stem cell differentiation. However, little is known about how these niches are formed. Here, we report that off and on states of Hh signaling determine the fate of maintenance (cap cells) and differentiation niche (escort cells), respectively, of the Drosophila ovarian germline stem cell (GSC). During development, Hh signaling is activated in intermingled cells (ICs, niche precursors), while it is absent in cap cells but remained in escort cells. Suppressing Hh signaling turnover in ICs, results in cap cell reduction, and induces cap-escort transitional cells that eventually shift toward the escort cell lineage. We also report that Hh signaling in cap cells is silenced via Notch signaling and Cullin3 (Cul3)-HIB-mediated proteasome in a parallel or an upstream-downstream manner. From a small-scale RNAi screening for Cul3 regulators combined with the in silico promoter analysis, we find that the promoter of Ubc10, an E2 ubiquitin-conjugating enzyme, carries two putative Notch responsive elements, and Ubc10 knockdown in ICs phenocopies the above-described phenotypes. Interestingly, Ubc10 with its E3 partner, Ari-1 (Ari-1-Ubc10) is proposed to coordinate with Cul3-HIB complex for protein degradation, an E3-E3 tagging model. Although more studies are needed to pinpoint the involved mechanisms, our studies have added knowledge on the establishment of stem cell niches, and that may be applied to other stem cell systems.