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The zebrafish atrioventricular (AV) valve transitions from 2-cusp to 4-cusp at 14 days post-fertilization (dpf) through commissural remodeling, differential cell proliferation, and chondrogenic matrix secretion. Orthogonal valvular axes are present at 25 hpf (hours), preceding endocardial cushion formation. AV canal remodeling aligns the shear stress with leaflet formation at 48 hpf and 14 dpf. At 28 hpf, the ventricle develops functional syncytium, while the atrial peristalsis remains and is necessary for the Klf2a-Snai1b signaling in Notch-negative and\n                  <jats:italic>ccm1<\/jats:italic>\n                  -positive endocardial cells. Without atrial contraction, the 2-to 4-cusp transition (86.7%) fails to occur. In the absence of ventricular contraction and relaxation, the formation of the first pair of leaflets (100%) does not initiate. As a corollary, we demonstrate that KLF4\/SNAI1 expression at the commissure is conserved in the mammalian AV 2- to 4-cushion transition.\n                <\/jats:p>","DOI":"10.64898\/2026.05.04.722768","type":"posted-content","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:00:18Z","timestamp":1778220018000},"source":"Crossref","is-referenced-by-count":0,"title":["A Continuum of Atrial Peristalsis Initiates the Bicuspid to Quadricuspid Valve Transition"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-5131","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Bioengineering, UCLA, Los Angeles, CA, USA"},{"name":"Division of Cardiology, Department of Medicine, School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Medicine, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-6189","authenticated-orcid":false,"given":"Aaron L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Medicine, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie Z.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA, USA"},{"name":"School of Medicine, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau-Nian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Yokota","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Medicine, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul-Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Medicine, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison L.","family":"Marsden","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Bioengineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzung K.","family":"Hsiai","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, UCLA, Los Angeles, CA, USA"},{"name":"Division of Cardiology, Department of Medicine, School of Medicine, UCLA, Los Angeles, CA, USA"},{"name":"Department of Medicine, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051113550624000_2026.05.04.722768v1.1","doi-asserted-by":"crossref","unstructured":"Small, A. 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