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

Published version
Peer-reviewed

Type

Article

Change log

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

D. melanogaster, developmental biology, gastrulation, live-imaging, notch, tissue-mechanics, transcription, Animals, Drosophila, Gastrulation, Gene Expression Regulation, Developmental, Mesoderm, Morphogenesis, Receptors, Notch, Signal Transduction

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)