YAP regulates cell size and growth dynamics via non-cell autonomous mediators
Abstract
The Hippo pathway regulates organ size, regeneration, and cell growth by controlling the stability of the transcription factor, YAP (Yorkie in Drosophila). When there is tissue damage, YAP is activated allowing the restoration of homeostatic tissue size. The exact signals by which YAP is activated are still not fully understood, but its activation is known to affect both cell size and cell number. Here we used cultured cells to examine the coordinated regulation of cell size and number under the control of YAP. Our experiments in isogenic HEK293 cells reveal that YAP can affect cell size and number by independent circuits. Some of these effects are cell autonomous, such as proliferation, while others are mediated by secreted signals. In particular CYR61, a known secreted YAP target, is a non-cell autonomous mediator of cell survival, while another unidentified secreted factor controls cell size.
Data availability
Sequencing data has been deposited in GEO under accession code GSE123296
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Induction of YAP5SA-GFP vs nGFP expression in FlipinTrex293 cellsNCBI Gene Expression Omnibus, GSE123296.
Article and author information
Author details
Funding
Harvard Medical School (Dean's Innovation Grant)
- Marc W Kirschner
National Institute of General Medical Sciences (GM026875)
- Marc W Kirschner
Eunice Kennedy Shriver National Institute of Child Health and Human Development (9R01HD091846-05A1)
- Marc W Kirschner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Duojia Pan, UT Southwestern Medical Center and HHMI, United States
Version history
- Received: November 7, 2019
- Accepted: December 16, 2019
- Accepted Manuscript published: January 8, 2020 (version 1)
- Accepted Manuscript updated: January 9, 2020 (version 2)
- Version of Record published: January 29, 2020 (version 3)
- Version of Record updated: January 30, 2020 (version 4)
Copyright
© 2020, Mugahid et al.
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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