Spatio-temporal control of nuclear mechanotransduction during EMT

Bouzignac, R.; Palandri, A.; Zine el Aabidine, A.; Mangeat, T.; Merle, T.; Cazales, M.; Trullo, A.; Rouviere, C.; Pimmett, V.; Lagha, M. L.; Suzanne, M.

doi:10.1101/2025.08.25.672162

bioRxiv · 10.1101/2025.08.25.672162

Spatio-temporal control of nuclear mechanotransduction during EMT

Bouzignac, R.·Palandri, A.·Zine el Aabidine, A.·Mangeat, T.·Merle, T.·Cazales, M.·Trullo, A.·Rouviere, C.·Pimmett, V.·Lagha, M. L.·Suzanne, M.

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Abstract

During epithelial-to-mesenchymal transition (EMT), cells generate mechanical forces. How the nucleus reacts to these mechanical cues, ensuring a tight balance between mechano-protection and mechanotransduction, is a key yet unresolved question. Here we dissect the spatio-temporal control of nuclear mechanostransduction during EMT, using Drosophila mesoderm invagination as a model. We found that two conserved pro-EMT genes respond differently to compressive forces: while snail transcription remains unaffected, compression is sufficient to activate twist transcription within seconds. We further revealed a spatially patterned genome-wide transcriptional response to EMT forces, with an apical mechanoprotection contrasting with a permissive basal nuclear environment. The direct recording of nascent transcription in response to a controlled nuclear micromanipulation provides compelling evidence of nuclear heterogeneity in the transcriptional response to forces. Overall, these results reveal that EMT nuclei respond directly and rapidly to mechanical forces, in a spatially defined pattern.

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Bouzignac, R., Palandri, A., Zine el Aabidine, A., Mangeat, T., Merle, T., Cazales, M., Trullo, A., Rouviere, C., Pimmett, V., Lagha, M. L., Suzanne, M.. 2025-08-25. Spatio-temporal control of nuclear mechanotransduction during EMT. https://doi.org/10.1101/2025.08.25.672162

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