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bioRxiv · 10.64898/2026.02.10.705054

To Be or Not to Be an Oocyte: Msps/XMAP215 Controls Oocyte Cell Fate in the Drosophila Ovary

Lu, W.·Lakonishok, M.·Neiswender, H.·Gonsalvez, G. B.·Gelfand, V. I.
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Abstract

Cell fate determination, the process by which cells commit to specific identities, is fundamental to development. Oocyte specification in Drosophila provides an excellent model to dissect these molecular mechanisms. In the Drosophila ovary, 16 interconnected germline cells arise through four mitotic divisions with incomplete cytokinesis. Among them, the two oldest cells become pro-oocytes, and one is selected to develop into the oocyte while maintaining diploidy; the remaining 15 differentiate into nurse cells and enter endoreplication. Previously, we showed that Mini spindles (Msps), a microtubule polymerase and homolog of XMAP215, is essential for oocyte maintenance. Here, we report that Msps/XMAP215 is expressed early in development, with both mRNA and protein enriched in the pro-oocytes prior to oocyte specification. Knockdown of Msps prevents oocyte specification, leading to egg chambers with 16 nurse cells. Loss of Msps also disrupts the accumulation of the oocyte marker Orb and the microtubule minus-end binding protein Patronin/CAMSAP, both critical for oocyte specification. Remarkably, optogenetic recruitment of Msps is sufficient to increase microtubule polymerization and promote Orb accumulation in nurse cells, suggesting that Msps activity is sufficient to drive oocyte fate determination. Furthermore, we show that Msps associates with the germline-specific organelles, spectrosome and fusome, and becomes asymmetrically distributed among sister cells, allowing the two pro-oocytes to inherit higher levels of Msps than their siblings. Together, we propose a model in which Msps-mediated microtubule polymerization provides the pro-oocyte with a competitive advantage, initiating a positive feedback loop that involves dynein-dependent transport of msps mRNA to reinforce oocyte specification. TeaserA self-reinforcing cytoskeletal feedback loop selects a single egg cell from a cluster of interconnected germ cells.

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Lu, W., Lakonishok, M., Neiswender, H., Gonsalvez, G. B., Gelfand, V. I.. 2026-02-11. To Be or Not to Be an Oocyte: Msps/XMAP215 Controls Oocyte Cell Fate in the Drosophila Ovary. https://doi.org/10.64898/2026.02.10.705054

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