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However, in vertebrates, little is known about its homolog Llgl1. Here, we define a novel role for vertebrate Llgl1 in regulating Yap stability in cardiomyocytes, which impacts heart development. In contrast to the role of Drosophila L(2)gl, Llgl1 depletion in cultured rat cardiomyocytes decreased Yap protein levels and blunted target gene transcription without affecting Yap transcript abundance. Llgl1 depletion in zebrafish resulted in larger and dysmorphic cardiomyocytes, pericardial effusion, impaired blood flow and aberrant valvulogenesis. Cardiomyocyte Yap protein levels were decreased in llgl1 morphants, whereas Notch, which is regulated by hemodynamic forces and participates in valvulogenesis, was more broadly activated. Consistent with the role of Llgl1 in regulating Yap stability, cardiomyocyte-specific overexpression of Yap in Llgl1-depleted embryos ameliorated pericardial effusion and restored blood flow velocity. Altogether, our data reveal that vertebrate Llgl1 is crucial for Yap stability in cardiomyocytes and its absence impairs cardiac development.<\/jats:p>","DOI":"10.1242\/dev.193581","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T14:55:14Z","timestamp":1598367314000},"source":"Crossref","is-referenced-by-count":15,"title":["Llgl1 regulates zebrafish cardiac development by mediating Yap stability in cardiomyocytes"],"prefix":"10.1242","volume":"147","author":[{"given":"Michael A.","family":"Flinn","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy, Medical\u2008College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Otten","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Biology, University of Potsdam, 14476 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary J.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy, Medical\u2008College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Bostrom","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy, Medical\u2008College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aria","family":"Kenarsary","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy, Medical\u2008College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Genomics Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina C.","family":"Wan","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Auchampach","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Abdelilah-Seyfried","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Biology, University of Potsdam, 14476 Potsdam, Germany"},{"name":"Institute for Molecular Biology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin C.","family":"O'Meara","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Genomics Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-2642","authenticated-orcid":false,"given":"Brian A.","family":"Link","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy, Medical\u2008College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"2021042622524808800_DEV193581C1","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1016\/j.bbamcr.2016.03.004","article-title":"Interplay between cardiac function and heart development","volume":"1863","author":"Andr\u00e9s-Delgado","year":"2016","journal-title":"Biochim. 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