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Development. 2018 Mar 8;145(5). pii: dev159467. doi: 10.1242/dev.159467.

Mechanical strain regulates the Hippo pathway in Drosophila.

Author information

1
Epithelial Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
2
Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
3
Epithelial Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK barry.thompson@crick.ac.uk.

Abstract

Animal cells are thought to sense mechanical forces via the transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1), the sole Drosophila homolog of which is named Yorkie (Yki). In mammalian cells in culture, artificial mechanical forces induce nuclear translocation of YAP and TAZ. Here, we show that physiological mechanical strain can also drive nuclear localisation of Yki and activation of Yki target genes in the Drosophila follicular epithelium. Mechanical strain activates Yki by stretching the apical domain, reducing the concentration of apical Crumbs, Expanded, Kibra and Merlin, and reducing apical Hippo kinase dimerisation. Overexpressing Hippo kinase to induce ectopic activation in the cytoplasm is sufficient to prevent Yki nuclear localisation even in flattened follicle cells. Conversely, blocking Hippo signalling in warts clones causes Yki nuclear localisation even in columnar follicle cells. We find no evidence for involvement of other pathways, such as Src42A kinase, in regulation of Yki. Finally, our results in follicle cells appear generally applicable to other tissues, as nuclear translocation of Yki is also readily detectable in other flattened epithelial cells such as the peripodial epithelium of the wing imaginal disc, where it promotes cell flattening.

KEYWORDS:

Cell shape; Drosophila; Hippo pathway; Mechanosensing; Yorkie

PMID:
29440303
PMCID:
PMC5868995
DOI:
10.1242/dev.159467
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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