{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T07:38:20Z","timestamp":1774251500128,"version":"3.50.1"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370353 and 82100321"],"award-info":[{"award-number":["82370353 and 82100321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"\n Abnormal cardiac valve development may lead to functional impairment in adulthood.\n BMPR2<\/jats:italic>\n , a highly conserved receptor of the BMP family, exists in two subtypes (\n bmpr2a<\/jats:italic>\n and\n bmpr2b<\/jats:italic>\n ) in zebrafish. However, the roles of\n bmpr2a<\/jats:italic>\n and\n bmpr2b<\/jats:italic>\n in valve development remain unclear. In this study, we generated three\n bmpr2a\/b<\/jats:italic>\n mutant zebrafish strains, namely,\n bmpr2a<\/jats:italic>\n - and\n bmpr2b<\/jats:italic>\n -knockout zebrafish (\n bmpr2a<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n bmpr2b<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n , respectively) using CRISPR\/Cas9 and\n bmpr2a<\/jats:italic>\n and\n bmpr2b<\/jats:italic>\n double-knockout zebrafish (\n bmpr2a<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;bmpr2b<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ) according to\n bmpr2a<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and\n bmpr2b<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n hybridization. Using cardiac function assessment (M-mode), we characterized the cardiac developmental phenotypes of the three zebrafish mutant strains. Transcriptomic profiling (RNA-seq) was combined with whole-mount\n in situ<\/jats:italic>\n hybridization (WISH) and qRT-PCR to validate gene-expression changes. The results indicated that\n bmpr2a<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ,\n bmpr2b<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n , and\n bmpr2a<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ;bmpr2b<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mutant zebrafish strains exhibited valve developmental defects at 52\u00a0hours post-fertilization (hpf), followed by cardiac contractile dysfunction. RNA-seq revealed upregulation of cardiac markers (\n myl9a<\/jats:italic>\n ,\n myl9b<\/jats:italic>\n ,\n tnnc1a<\/jats:italic>\n ,\n cmlc1<\/jats:italic>\n ,\n myl7<\/jats:italic>\n , and\n nppa<\/jats:italic>\n ) and valve-related genes (\n fn1b<\/jats:italic>\n ,\n has2<\/jats:italic>\n , and\n nfatc1<\/jats:italic>\n ), along with the downregulation of\n klf2a<\/jats:italic>\n , as validated by WISH and qRT-PCR. Pathway analysis identified the ECM-receptor interaction as a key regulatory axis of\n bmpr2a\/b<\/jats:italic>\n -mediated valve development. In this study, we demonstrate that\n bmpr2a<\/jats:italic>\n and\n bmpr2b<\/jats:italic>\n cooperatively regulate cardiac contractile function and valve development in zebrafish, providing insights into BMPR2-mediated cardiovascular morphogenesis in humans.\n <\/jats:p>","DOI":"10.3389\/fcell.2026.1652622","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:44:05Z","timestamp":1774248245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BMPR2 affects valve development via ECM\u2013receptor interaction in zebrafish"],"prefix":"10.3389","volume":"14","author":[{"given":"Yan","family":"Shi","sequence":"first","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Key Laboratory of South China 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Pathogenesis, Targeted Prevention and Treatment of Heart Disease, Guangzhou Key Laboratory of Cardiac Pathogenesis and Prevention","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiushan","family":"Wu","sequence":"additional","affiliation":[{"name":"The Laboratory of Heart Development Research, College of Life Science, Hunan Normal 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