Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation.
eLife Sciences Publications, Ltd
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Falo-Sanjuan, J., & Bray, S. (2022). Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation.. Elife, 11 https://doi.org/10.7554/eLife.73656
Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination between mechanical forces from morphogenesis and cell-cell signalling to confer appropriate changes in gene expression. By live-imaging Notch-induced transcription in real time, we have discovered that morphogenetic movements during Drosophila gastrulation bring about an increase in activity-levels of a Notch-responsive enhancer. Mutations that disrupt the timing of gastrulation resulted in concomitant delays in transcription up-regulation that correlated with the start of mesoderm invagination. As a similar gastrulation-induced effect was detected when transcription was elicited by the intracellular domain NICD, it cannot be attributed to forces exerted on Notch receptor activation. A Notch-independent vnd enhancer also exhibited a modest gastrulation-induced activity increase in the same stripe of cells. Together, these observations argue that gastrulation-associated forces act on the nucleus to modulate transcription levels. This regulation was uncoupled when the complex linking the nucleoskeleton and cytoskeleton (LINC) was disrupted, indicating a likely conduit. We propose that the coupling between tissue-level mechanics, arising from gastrulation, and enhancer activity represents a general mechanism for ensuring correct tissue specification during development and that Notch-dependent enhancers are highly sensitive to this regulation.
Transcription, Gastrulation, Notch, developmental biology, Live-imaging, D. Melanogaster, Tissue-mechanics, Mesoderm, Animals, Drosophila, Signal Transduction, Gene Expression Regulation, Developmental, Morphogenesis, Receptors, Notch
Wellcome Trust (212207/Z/18/Z)
Wellcome Trust (102175/B/13/Z)
Wellcome Trust (109144/Z/15/Z)
External DOI: https://doi.org/10.7554/eLife.73656
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338424
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/