title: Chondroitin sulfate expression is required for cardiac atrioventricular canal formation.
abstract: Defects in cardiac valvulogenesis are a common cause of congenital heart disease, and the study of this process promises to provide mechanistic insights and lead to novel therapeutics. Normal valve development involves multiple signaling pathways, and recently roles have been identified for extracellular matrix components, including glycosaminoglycans. We, therefore, explored the role of the glycosaminoglycan chondroitin sulfate during zebrafish cardiac development. Beginning at 33 hr, there is a distinct zone of chondroitin sulfate expression in the atrioventricular (AV) boundary, in the cardiac jelly between the endocardium and myocardium. This expression is both spatially and temporally restricted, and is undetectable after 48 hr. Chemical as well as genetic inhibition of chondroitin synthesis results in AV canal (AVC) defects, including loss of the atrioventricular constriction, blood regurgitation, and failure of circulation. Lack of chondroitin disrupts a marker of cell migration, results in a loss of myocardial and endothelial markers of valvulogenesis, and misregulates bone morphogenetic protein expression, supporting an early role in AVC development. In summary, we have defined a requirement for chondroitin sulfate expression in the normal patterning of the AV boundary, suggesting that this component of the cardiac jelly provides a necessary signal in this critical transition in vertebrate cardiogenesis.
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Cardiovascular Research Center and Cardiology Division, Charlestown, Massachusetts, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Peal
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Burns
authors.forename: Calum A
authors.initials: CA
authors.lastname: Macrae
authors.forename: David
authors.initials: D
authors.lastname: Milan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000502:physiology; D004694:Endocardial Cushion Defects / Q000235:genetics / Q000378:metabolism; D054089:Endocardial Cushions / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D004699:Endocardium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D009206:Myocardium / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D002809:Chondroitin Sulfates; D017350:N-Acetylgalactosaminyltransferases; C412725:chondroitin synthase