Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation

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Abstract

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.

Data availability

Source data files are provided for each plot in each figure.Code used for data analysis is available on GitHub:https://github.com/BrayLab/LiveTrxRaw movies and analysis files have been deposited in two FigShare repositories:https://doi.org/10.6084/m9.figshare.16619773.v45https://doi.org/10.6084/m9.figshare.19697413.v2

The following data sets were generated

1. Falo Sanjuan J
2. Bray
3. SJ
(2022) MS2 data from 'Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation'
figshare, https://doi.org/10.6084/m9.figshare.16619773.v45.

https://doi.org/10.6084/m9.figshare.16619773.v45
1. Falo Sanjuan J
2. Bray SJ
(2022) Other data from 'Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation'
figshare, https://doi.org/10.6084/m9.figshare.19697413.v2.

https://doi.org/10.6084/m9.figshare.19697413.v2

Article and author information

Author details

Julia Falo-Sanjuan

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3563-4789
Sarah Bray

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

For correspondence
sjb32@cam.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1642-599X

Funding

Wellcome Trust (212207/Z/18/Z)

Sarah Bray

Medical Research Council (MR/T014156/1)

Sarah Bray

Wellcome Trust (109144/Z/15/Z)

Julia Falo-Sanjuan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.