sox9b is required in cardiomyocytes for cardiac morphogenesis and function

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ID: 103946
2018
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Abstract
Abstract The 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.
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gawdzik2018sox9bscientific Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Gawdzik, Joseph C.;Yue, Monica S.;Martin, Nathan R.;Elemans, Loes M. H.;Lanham, Kevin A.;Heideman, Warren;Rezendes, Ryan;Baker, Tracie R.;Taylor, Michael R.;Plavicki, Jessica S.;
Journal Scientific reports
Year 2018
DOI
DOI not found
URL
http://link.springer.com/article/10.1038/s41598-018-32125-7
Keywords
chemistry Biology (General) Medicine Science evolution

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