Spatio-temporal control of nuclear mechanotransduction during Epithelial-to-Mesenchymal Transition

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.