Regulators of Contact Stimulation of Migration in Testis Nascent Myotubes
Cell Biology
Final Report Abstract
The testis nascent myotube migration system is an in vivo model for collective cell migration in Drosophila that I established during my PhD thesis. During the funding period, I published a protocol paper to enable the scientific community to adopt it. Furthermore, I acquired testis myotube-specific transcriptomic data that I analyzed and used to perform a large-scale RNAi screen for potential regulators of collective cell migration. One of the most interesting hits was the axon guidance factor Plexin A. Its genetic knockdown causes characteristic gaps in the testis muscle sheet that arise during the collective cell migration of myotubes. Depleting its antagonist Semaphorin 1B interestingly yields similar-looking gaps in the adult animal. Using high-resolution 4D live cell imaging, different genetic perturbations, live-markers for multiple cytoskeletal and cell-adhesion components, and genetic interaction assays, I analyzed the function of PlexA signalling in enabling testis nascent myotubes to migrate as a continuous mesenchymal cell sheet. Tissue-specific expression of plexARNAi drastically alters the architecture of cells. They become less mesenchymal and adhesive to the substrate, and more epithelial with more stable cell-cell contacts. This results in the formation of tall cell clusters that perturb migration. Reducing sema1B and overexpressing a non-inactivatable PlexA both cause an opposing effect, with the weakening of cell-cell adhesions resulting in similar-looking gaps. Our findings suggest that fine-tuning of PlexA signalling – which acts in this system via Ras2 – is crucial to maintaining the correct ratio of protrusion and adhesion, enabling cells to migrate as a continuous uninterrupted sheet. These findings are highly relevant to understand how migrating groups of cells avoid gaps, which is for example crucial for endothelial migration during angio- and vasculogenesis and regeneration.
Publications
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cell bio 2022 by ASCB, Washington DC, United States, December 2022, Poster: Contact Stimulation of Collective Migration as a Novel Driver in Tissue Morphogenesis
Maik Bischoff
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Cell biology: Keeping the epithelium together when your neighbor divides. Current Biology, 32(20), R1025-R1027.
Bischoff, Maik C. & Peifer, Mark
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Triangle Cytoskeleton Meeting, Durham, United States, September 2022, Poster: Contact Stimulation of Collective Migration as a Novel Driver in Tissue Morphogenesis
Maik Bischoff
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Dissecting Collective Cell Behavior in Migrating Testis Myotubes in Drosophila. Methods in Molecular Biology, 117-129. Springer US.
Bischoff, Maik C. & Bogdan, Sven
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Triangle Fly Symposium, Durham, United States, May 2023, Talk: Plexin/Semaphorin-signalling ensures follower-motility in collective cell migration
Maik Bischoff
