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Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10347-52. doi: 10.1073/pnas.1409233111. Epub 2014 Jun 23.

Piezo1, a mechanically activated ion channel, is required for vascular development in mice.

Author information

1
Howard Hughes Medical Institute andDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037;
2
Howard Hughes Medical Institute andDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037;Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; and.
3
Department of Bioengineering andInstitute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92032.
4
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; and.
5
Department of Bioengineering andInstitute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92032 shuchien@ucsd.edu ardem@scripps.edu.
6
Howard Hughes Medical Institute andDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037; shuchien@ucsd.edu ardem@scripps.edu.

Abstract

Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.

PMID:
24958852
PMCID:
PMC4104881
DOI:
10.1073/pnas.1409233111
[Indexed for MEDLINE]
Free PMC Article

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