Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis
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Author(s)
Type
Journal Article
Abstract
Organ morphogenesis is driven by physical forces, yet how mechanical stimuli pattern tissue shape and guide developmental programs remains poorly understood. In zebrafish, endocardial cells (EdCs) within the heart valve-forming region undergo marked volume reduction during
early morphogenesis. Here, we uncover a hydraulics-based mechanism by which mechanical forces control EdC volume to direct cardiac development. We show that the mechanosensitive ion channel Piezo1 acts with the calcium-binding protein calmodulin (CaM) and the aquaporin Aqp8a.1 water channel to orchestrate EdC shrinkage. We find that Aqp8a.1 mediates cell volume loss by incorporating into the plasma membrane in response to mechanical stimulation, promoting heart looping and valve formation. Mechanistically, Piezo1 governs Aqp8a.1
through a dual mechanism. First, Piezo1 and CaM drive Aqp8a.1 plasma membrane incorporation, enabling rapid cell volume adjustments. Second, Piezo1 suppresses aqp8a.1 transcription via Notch1b signaling to prevent excessive shrinkage. Altogether, these findings reveal that mechanotransduction can dictate organ formation through dynamic cell volume regulation, uncovering a fundamental principle of morphogenesis.
early morphogenesis. Here, we uncover a hydraulics-based mechanism by which mechanical forces control EdC volume to direct cardiac development. We show that the mechanosensitive ion channel Piezo1 acts with the calcium-binding protein calmodulin (CaM) and the aquaporin Aqp8a.1 water channel to orchestrate EdC shrinkage. We find that Aqp8a.1 mediates cell volume loss by incorporating into the plasma membrane in response to mechanical stimulation, promoting heart looping and valve formation. Mechanistically, Piezo1 governs Aqp8a.1
through a dual mechanism. First, Piezo1 and CaM drive Aqp8a.1 plasma membrane incorporation, enabling rapid cell volume adjustments. Second, Piezo1 suppresses aqp8a.1 transcription via Notch1b signaling to prevent excessive shrinkage. Altogether, these findings reveal that mechanotransduction can dictate organ formation through dynamic cell volume regulation, uncovering a fundamental principle of morphogenesis.
Date Issued
2026-04-24
Date Acceptance
2026-01-29
Citation
Science Advances, 2026, 12 (17)
ISSN
2375-2548
Publisher
American Association for the Advancement of Science (AAAS)
Journal / Book Title
Science Advances
Volume
12
Issue
17
Copyright Statement
Copyright © 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Publication Status
Published
Article Number
eaea7025
Date Publish Online
2026-04-22