Fusome morphogenesis is sufficient to promote female germline stem cell self-renewal in Drosophila.

Many tissue-resident stem cells are retained through asymmetric cell division, a process that ensures stem cell self-renewal through each mitotic cell cycle. Asymmetric organelle distribution has been proposed as a mechanism by which stem cells are marked for long-term retention; however, it is not clear whether biased organelle localization is a cause or an effect of asymmetric division. In Drosophila females, an endoplasmic reticulum-like organelle called the fusome is continually regenerated in germline stem cells (GSCs) and associated with GSC division. Here, we report that the β-importin Tnpo-SR is essential for fusome regeneration. Depletion of Tnpo-SR disrupts cytoskeletal organization during interphase and nuclear membrane remodeling during mitosis. Tnpo-SR does not localize to microtubules, centrosomes, or the fusome, suggesting that its role in maintaining these processes is indirect. Despite this, we find that restoring fusome morphogenesis in Tnpo-SR-depleted GSCs is sufficient to rescue GSC maintenance and cell cycle progression. We conclude that Tnpo-SR functionally fusome regeneration to cell cycle progression, supporting the model that asymmetric rebuilding of fusome promotes maintenance of GSC identity and niche retention.