{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:16:38Z","timestamp":1778818598281,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T00:00:00Z","timestamp":1372809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects.<\/jats:p>","DOI":"10.3390\/ijms140713826","type":"journal-article","created":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T16:39:47Z","timestamp":1372869587000},"page":"13826-13841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Knockdown of FABP3 Impairs Cardiac Development in Zebra\ufb01sh through the Retinoic Acid Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Xuejie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Emergency, Subei People Hospital, Yangzhou, Jiangsu 225001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guixian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingmei","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University,  Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0031-3955(16)36830-4","article-title":"Congenital heart disease: Incidence and inheritance","volume":"37","author":"Hoffman","year":"1990","journal-title":"Pediatr. Clin. N. Am"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1161\/01.CIR.88.5.2479","article-title":"Report of the task force on children and youth. American Heart Association","volume":"88","author":"Moller","year":"1993","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nature06801","article-title":"The developmental genetics of congenital heart disease","volume":"451","author":"Bruneau","year":"2008","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.carpath.2007.06.005","article-title":"Genetic insights into normal and abnormal heart development","volume":"17","author":"Nemer","year":"2008","journal-title":"Cardiovasc. Pathol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/35025190","article-title":"A genetic blueprint for cardiac development","volume":"407","author":"Srivastava","year":"2000","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1093\/eurheartj\/ehn363","article-title":"Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T","volume":"29","author":"McCann","year":"2008","journal-title":"Eur. Heart J"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbrc.2006.01.113","article-title":"Identification of differentially expressed genes in human heart with ventricular septal defect using suppression subtractive hybridization","volume":"342","author":"Zhang","year":"2006","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10863-012-9439-y","article-title":"Silencing of FABP3 promotes apoptosis and induces mitochondrion impairment in embryonic carcinoma cells","volume":"44","author":"Shen","year":"2012","journal-title":"J. Bioenerg. Biomembr"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00441-004-0881-y","article-title":"Heart-type fatty acid binding proteins are upregulated during terminal differentiation of mouse cardiomyocytes, as revealed by proteomic analysis","volume":"316","author":"Tang","year":"2004","journal-title":"Cell. Tissue Res"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1126\/science.1101573","article-title":"Retinoic acid signaling restricts the cardiac progenitor pool","volume":"307","author":"Keegan","year":"2005","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/dvdy.21570","article-title":"Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway","volume":"237","author":"Sirbu","year":"2008","journal-title":"Dev. Dyn"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1242\/dev.00750","article-title":"A caudorostral wave of RALDH2 conveys anteroposterior information to the cardiac field","volume":"130","author":"Hochgreb","year":"2003","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/1097-0185(20001001)260:2<148::AID-AR50>3.0.CO;2-X","article-title":"Structure and function of the developing zebrafish heart","volume":"260","author":"Hu","year":"2000","journal-title":"Anat. Rec"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1242\/dev.124.11.2099","article-title":"Fashioning the vertebrate heart: Earliest embryonic decisions","volume":"124","author":"Fishman","year":"1997","journal-title":"Development"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/cvr\/cvr098","article-title":"Zebrafish as a model to study cardiac development and human cardiac disease","volume":"91","author":"Bakkers","year":"2011","journal-title":"Cardiovasc. Res"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1046\/j.1432-1033.2003.03705.x","article-title":"Structure, linkage mapping and expression of the heart-type fatty acid-binding protein gene (fabp3) from zebrafish (Danio rerio)","volume":"270","author":"Liu","year":"2003","journal-title":"Eur. J. Biochem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1111\/j.1742-4658.2007.05711.x","article-title":"The fabp4 gene of zebrafish (Danio rerio)\u2014Genomic homology with the mammalian FABP4 and divergence from the zebrafish fabp3 in developmental expression","volume":"274","author":"Liu","year":"2007","journal-title":"FEBS J"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/79951","article-title":"Effective targeted gene \u2018knockdown\u2019 in zebrafish","volume":"26","author":"Nasevicius","year":"2000","journal-title":"Nat. Genet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1242\/dev.124.21.4373","article-title":"Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish","volume":"124","author":"Chen","year":"1997","journal-title":"Development"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1242\/dev.030924","article-title":"Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart","volume":"136","author":"Clijsters","year":"2009","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/327625a0","article-title":"Identification and spatial distribution of retinoids in the developing chick limb bud","volume":"327","author":"Thaller","year":"1987","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6121","DOI":"10.1242\/dev.00838","article-title":"Mutation of weak atrium\/atrial myosin heavy chain disrupts atrial function and influences ventricular morphogenesis in zebrafish","volume":"130","author":"Berdougo","year":"2003","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1242\/dev.127.12.2573","article-title":"The bHLH transcription factor hand2 plays parallel roles in zebrafish heart and pectoral fin development","volume":"127","author":"Yelon","year":"2000","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1242\/dev.052225","article-title":"Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function","volume":"137","author":"Riley","year":"2010","journal-title":"Development"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1161\/CIRCRESAHA.109.194464","article-title":"Signaling pathways controlling second heart field development","volume":"104","author":"Rochais","year":"2009","journal-title":"Circ. Res"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1073\/pnas.0712344105","article-title":"Retinoic acid deficiency alters second heart field formation","volume":"105","author":"Ryckebusch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1093\/hmg\/ddl416","article-title":"Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick","volume":"15","author":"Roberts","year":"2006","journal-title":"Hum. Mol. Genet"},{"key":"ref_28","unstructured":"Westerfield, M. (1993). The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish Danio (Brachydanio) rerio, M. Westerfield."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nprot.2007.514","article-title":"High-resolution in situ hybridization to whole-mount zebrafish embryos","volume":"3","author":"Thisse","year":"2008","journal-title":"Nat. Protoc"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/dbio.1999.9406","article-title":"Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish","volume":"214","author":"Yelon","year":"1999","journal-title":"Dev. 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