|ZFIN ID: ZDB-PUB-091120-23|
Chondroitin sulfate expression is required for cardiac atrioventricular canal formation
Peal, D.S., Burns, C.G., MacRae, C.A., and Milan, D.
|Source:||Developmental dynamics : an official publication of the American Association of Anatomists 238(12): 3103-3110 (Journal)|
|Registered Authors:||Burns, Geoff, MacRae, Calum A., Milan, David J.|
|Keywords:||cardiac valve, cardiac development, chondroitin sulfate, extracellular matrix, cardiac jelly, epithelial to mesenchymal transition, Zebrafish|
|PubMed:||19890913 Full text @ Dev. Dyn.|
Peal, D.S., Burns, C.G., MacRae, C.A., and Milan, D. (2009) Chondroitin sulfate expression is required for cardiac atrioventricular canal formation. Developmental dynamics : an official publication of the American Association of Anatomists. 238(12):3103-3110.
ABSTRACTDefects 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.