{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:01:16Z","timestamp":1778864476075,"version":"3.51.4"},"reference-count":45,"publisher":"The Company of Biologists","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL095783"],"award-info":[{"award-number":["R01HL095783"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. Here, we specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1 deletion caused congenital mitral valve stenosis and regurgitation, whereas it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.<\/jats:p>","DOI":"10.1242\/jcs.259783","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T05:24:08Z","timestamp":1660109048000},"source":"Crossref","is-referenced-by-count":10,"title":["Differential requirement for DICER1 activity during the development of mitral and tricuspid valves"],"prefix":"10.1242","volume":"135","author":[{"given":"Shun","family":"Yan","sequence":"first","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"},{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia at Augusta University 2 , Augusta, GA 30912 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Peng","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Lu","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Shakil","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"},{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia at Augusta University 2 , Augusta, GA 30912 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Shi","sequence":"additional","affiliation":[{"name":"Medical College of Georgia at Augusta University 3 Department of Population Health Science, and Department of Neuroscience & Regenerative Medicine , , Augusta, GA 30912 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David K.","family":"Crossman","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Walter H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"},{"name":"The University of Alabama at Birmingham 4 Department of Pediatrics , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanrun","family":"Liu","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 5 Department of Biochemistry and Molecular Genetics , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald G.","family":"Rokosh","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 6 Division of Cardiovascular Disease, Department of Medicine , , Birmingham, AL 35294 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Lincoln","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin 7 Department of Pediatrics , , Milwaukee, WI 53226 , USA"},{"name":"The Herma Heart Institute 8 , Division of Pediatric Cardiology , , Milwaukee, WI 53226 , USA"},{"name":"Children's Wisconsin 8 , Division of Pediatric Cardiology , , Milwaukee, WI 53226 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 9 Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 , USA"},{"name":"Medical College of Georgia at Augusta University 10 Department of Neuroscience & Regenerative Medicine , , August, GA 30912 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-9020","authenticated-orcid":false,"given":"Kai","family":"Jiao","sequence":"additional","affiliation":[{"name":"The University of Alabama at Birmingham 1 Department of Genetics , , Birmingham, AL 35294 , USA"},{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia at Augusta University 2 , Augusta, GA 30912 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"2022090713404409200_JCS259783C1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1161\/01.RES.0000141146.95728.da","article-title":"Heart valve development: endothelial cell signaling and differentiation","volume":"95","author":"Armstrong","year":"2004","journal-title":"Circ. 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