{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:21:43Z","timestamp":1792228903074,"version":"4.4.0"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"17","funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Bioimaging Technology Development Awards 2024"],"award-info":[{"award-number":["Bioimaging Technology Development Awards 2024"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Early-Career Award, grant no. 313345\/Z\/24\/Z"],"award-info":[{"award-number":["Early-Career Award, grant no. 313345\/Z\/24\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["GA682938"],"award-info":[{"award-number":["GA682938"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/Y00566X\/1"],"award-info":[{"award-number":["BB\/Y00566X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Additional Ventures Single Ventricle Research Fund"},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["MR\/X019837\/1"],"award-info":[{"award-number":["MR\/X019837\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"JSPS Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["22H02624, 22H05168"],"award-info":[{"award-number":["22H02624, 22H05168"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"RIKEN BDR-Otsuka Pharmaceutical Collaboration Center"},{"name":"JSPS KAKENHI","award":["22K06244"],"award-info":[{"award-number":["22K06244"]}]},{"DOI":"10.13039\/501100006264","name":"RIKEN","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation,","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Royal Society Wolfson Research Merit Award."}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"<jats:p>\n                    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\u2013forming 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\n                    <jats:italic toggle=\"yes\">aqp8a.1<\/jats:italic>\n                    transcription via Notch1b signaling to prevent excessive shrinkage. Together, these findings reveal that mechanotransduction can dictate organ formation through dynamic cell volume regulation, uncovering a fundamental principle of morphogenesis.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea7025","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:59:52Z","timestamp":1776880792000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-2267","authenticated-orcid":true,"given":"Christina","family":"Vagena-Pantoula","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."},{"name":"The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-8905","authenticated-orcid":true,"given":"Konstantinos","family":"Kalyviotis","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."},{"name":"The Francis Crick Institute, London, UK."},{"name":"Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."},{"name":"Department of Structural Heart Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7474-0800","authenticated-orcid":true,"given":"Antoine","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."},{"name":"The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-7291","authenticated-orcid":true,"given":"Igor","family":"Kondrychyn","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Morphogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8081-1353","authenticated-orcid":true,"given":"Moe","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-4414","authenticated-orcid":true,"given":"Xiangbin","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Structural Heart Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-3717","authenticated-orcid":true,"given":"Thomas","family":"Juan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0382-0026","authenticated-orcid":true,"given":"Didier Y. R.","family":"Stainier","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Germany."},{"name":"Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8367-9332","authenticated-orcid":true,"given":"Periklis","family":"Pantazis","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8523-9958","authenticated-orcid":true,"given":"Li-Kun","family":"Phng","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Morphogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8924-732X","authenticated-orcid":true,"given":"Julien","family":"Vermot","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK."},{"name":"The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.008"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122340"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.052"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2022.04.021"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39596"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1309-x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw7709"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37131"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.11.025"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4206"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41567-021-01235-x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001505"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6229"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.02.011"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036723"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.131425"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000246"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.11.014"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11646"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.152124"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.03.038"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44706"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.09.023"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35843-3"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01970"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu186"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl0633"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.03.013"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.086090"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4226"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20082039"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012867108"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.1.F13"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020303"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2021.183853"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.98612"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.037"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.95873"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1398236"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.329219"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.031"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.024"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207525200"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207339200"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.09.017"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng875"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.128"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2630"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011320027914"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07370"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40134-y"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080179"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.06.003"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2024.11.005"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.151282"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19308-5"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.06.011"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.050"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1987-15.2015"},{"key":"e_1_3_2_61_2","doi-asserted-by":"crossref","unstructured":"Z.-Y. Yu S. Kesteven D. Cheng H. Lei J. Wu E. Nadar P. Macdonald M. Xaymardan C. D. Cox M. P. Feneley B. Martinac Deletion of PIEZO1 in adult cardiomyocytes accelerates cardiac aging and causes premature death. bioRxiv 633994 [Preprint] (2025). https:\/\/doi.org\/10.1101\/2025.01.20.633994.","DOI":"10.1101\/2025.01.20.633994"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/life14121688"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1080\/ann.34.3.192.200"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/2049-6958-9-29"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-011-8186-0"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.048785"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11805"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06489"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165589"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.514"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27249-w"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aea7025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:14:46Z","timestamp":1776957286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aea7025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":72,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,4,24]]}},"alternative-id":["10.1126\/sciadv.aea7025"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aea7025","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"2025-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaea7025"}}