INDIVIDUAL RESEARCHERJohn J. Schwarz , Ph.D.
Education- Ph.D. from University of Texas, Graduate School of Biomedical
Transcriptional Regulation of Cardiovascular Development
Wild type and mef2c null heart
My laboratory is interested in transcriptional regulation in the cardiovascular system during embryonic development. We have focused on members of the MEF2 family of transcription factors. These factors are postulated to function in muscle-specific gene expression and transduction of extracellular signals. One member in particular, EF2C, is among the first genes expressed during heart morphogenesis and is later expressed in the endothelial and vascular smooth muscle cells of blood vessels. We have deleted its gene in mice in order to understand its function in these cell types. Loss of MEF2C leads to hearts with an extremely small left ventricle and no right ventricle. The vascular system is also severely malformed.The major vessels of the embryo are very small and irregularly shaped in the region dorsal to the heart whereas they become grossly dilated posterior to the heart and in the head. These complex vascular malformations have many features in common with a known defect in an endothelial-specific growth factor, so a possible mechanisms for this phenotype is that the endothelial cells are unable to respond to this growth factors signal in the absence of MEF2C or that they control the transcription of some of the same genes. We intend to investigate the molecular defects in this mutant further to gain an understanding of the mechanisms by which cardiac chambers are specified and the vascular system is formed. Identifying the genes that are the downstream targets of MEF2C is a primary objective in this investigation.
- Weizhen B, Drake CJ, and Schwarz JJ: The Transcription Factor MEF2C-Null Mouse Exhibits Complex Vascular Malformations and Reduced Cardiac Expression of Angiopoietin 1 and VEGF. Dev. Biol. 211(2):255-267, 1999.
- Lin Q., Schwarz J.J., Bucana C., Olson E.N.: Control of Mouse Cardiac Morphogenesis and Myogenesis by Transcription Factor MEF2C. Science 276: 1404-1407, 1997.
- A.B. Firulli, J.M. Miano, W. Bi, D. Johnson, S.W. Casscells, E.N. Olson and J.J. Schwarz. Myocyte enhancer-binding factor-2 expression and activity in vascular smooth muscle cells: Association with the activated phenotype. Circ. Res. 78:196-204. 1996.
- G.E. Lyons, B.K. Micales, J. Schwarz, J.F. Martin and E.N. Olson. Expression of MEF2 genes in the mouse central nervous system suggests a role in neuronal maturation. J. Neuroscience 15(8):5727-5738. 1995.