View Program - 63rd Annual Drosophila Research Conference

Drosophila male germline stem cells (GSCs) divide asymmetrically to generate a self-renewing stem cell and a differentiating cell. The outcome of asymmetric division is compromised when cells that once initiated differentiation program revert back to stem cell state (i.e., dedifferentiation). Dedifferentiation has been proven to be an essential mechanism for the maintenance of the GSC pool. However, compromised asymmetric outcome may result in the clonal expansion/depletion of stem cells, leading to various pathological conditions. Therefore, the process of dedifferentiation must be carefully regulated. In this study, we characterized the process and outcome of dedifferentiation to understand the underlying mechanisms. By experimentally inducing a GSC-loss and recovery cycle in the testis, we found that the dedifferentiated GSCs reestablish the patch-like structure of a polarity protein, Bazooka (Baz, Drosophila homolog of mammalian Par-3), at the hub-GSC interface quickly within 1 to 3 days after induced GSC loss. Moreover, we found that differentiating spermatogonia start expressing Baz prior to migration to the niche, which suggests a role of Baz in the regulation of the dedifferentiation process. Baz has been shown to be required for stem cell-specific polarity checkpoint, centrosome orientation checkpoint (COC). Consistent with the quick recovery of Baz-patch, we observed the presence of intact centrosome orientation checkpoint, correct spindle orientation, and intact mitotic rates in dedifferentiated GSCs. Moreover, our live observation demonstrates that dedifferentiated GSC immediately divides after positioned back to the niche. Taken together, our results demonstrate that dedifferentiated GSCs quickly regain the ability to undergo asymmetric cell division and Baz plays an essential role in this process.

Function of Bazooka in dedifferentiation of the male germline stem cells