|ZFIN ID: ZDB-PUB-180919-2|
sox9b is required in cardiomyocytes for cardiac morphogenesis and function
Gawdzik, J.C., Yue, M.S., Martin, N.R., Elemans, L.M.H., Lanham, K.A., Heideman, W., Rezendes, R., Baker, T.R., Taylor, M.R., Plavicki, J.S.
|Source:||Scientific Reports 8: 13906 (Journal)|
|Registered Authors:||Heideman, Warren, Taylor, Michael R.|
|PubMed:||30224706 Full text @ Sci. Rep.|
Gawdzik, J.C., Yue, M.S., Martin, N.R., Elemans, L.M.H., Lanham, K.A., Heideman, W., Rezendes, R., Baker, T.R., Taylor, M.R., Plavicki, J.S. (2018) sox9b is required in cardiomyocytes for cardiac morphogenesis and function. Scientific Reports. 8:13906.
ABSTRACTThe high mobility group transcription factor SOX9 is expressed in stem cells, progenitor cells, and differentiated cell-types in developing and mature organs. Exposure to a variety of toxicants including dioxin, di(2-ethylhexyl) phthalate, 6:2 chlorinated polyfluorinated ether sulfonate, and chlorpyrifos results in the downregulation of tetrapod Sox9 and/or zebrafish sox9b. Disruption of Sox9/sox9b function through environmental exposures or genetic mutations produce a wide range of phenotypes and adversely affect organ development and health. We generated a dominant-negative sox9b (dnsox9b) to inhibit sox9b target gene expression and used the Gal4/UAS system to drive dnsox9b specifically in cardiomyocytes. Cardiomyocyte-specific inhibition of sox9b function resulted in a decrease in ventricular cardiomyocytes, an increase in atrial cardiomyocytes, hypoplastic endothelial cushions, and impaired epicardial development, ultimately culminating in heart failure. Cardiomyocyte-specific dnsox9b expression significantly reduced end diastolic volume, which corresponded with a decrease in stroke volume, ejection fraction, and cardiac output. Further analysis of isolated cardiac tissue by RT-qPCR revealed cardiomyocyte-specific inhibition of sox9b function significantly decreased the expression of the critical cardiac development genes nkx2.5, nkx2.7, and myl7, as well as c-fos, an immediate early gene necessary for cardiomyocyte progenitor differentiation. Together our studies indicate sox9b transcriptional regulation is necessary for cardiomyocyte development and function.