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

  1. Julia Falo-Sanjuan
  2. Sarah Bray  Is a corresponding author
  1. University of Cambridge, United Kingdom


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: movies and analysis files have been deposited in two FigShare repositories:

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Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3563-4789
  2. Sarah Bray

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1642-599X


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.

Reviewing Editor

  1. Danelle Devenport, Princeton University, United States

Publication history

  1. Received: September 6, 2021
  2. Preprint posted: September 16, 2021 (view preprint)
  3. Accepted: April 27, 2022
  4. Accepted Manuscript published: May 18, 2022 (version 1)
  5. Version of Record published: June 9, 2022 (version 2)


© 2022, Falo-Sanjuan & Bray

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.


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  1. Julia Falo-Sanjuan
  2. Sarah Bray
Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation
eLife 11:e73656.

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