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

Published version
Peer-reviewed

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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.

Description

Keywords

Research Article, Developmental Biology, notch, gastrulation, transcription, live-imaging, tissue-mechanics, D. melanogaster

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

11

Publisher

eLife Sciences Publications, Ltd
Sponsorship
MRC (MR/T014156/1)
Wellcome Trust (212207/Z/18/Z)
Wellcome Trust (102175/B/13/Z)
Wellcome Trust (109144/Z/15/Z)