Eric Svensson, M.D., Ph.D.

Transcriptional Regulation of Cardiac Development

Research Summary

My general research interest is to further our understanding of the transcriptional regulation of cardiac development with the expectation that this will lead to an improved understanding of the molecular basis of congenital heart disease.  Further, a more in-depth understanding of transcriptional pathways regulating cardiac development may generate novel paradigms that will be broadly applicable to the development of many other organ systems.  Finally, elucidation of the transcriptional regulation of heart formation may also suggest potential strategies to repair a heart damaged by a myocardial infarction and lead to novel insights into the origins of cardiac stem cells. 

Significant progress has been made in the last decade in elucidating the molecular mechanisms regulating cardiac morphogenesis, but this process is still only partially understood.  Many genes have now been identified that play a role in the transcriptional regulation of heart development.  Mutations in several of these genes have been shown to cause human congenital heart disease.  We have previously identified a gene critical for normal heart development called FOG-2, a member of the FOG family of transcriptional modulators that also includes FOG-1 and U-shaped.  FOG-2 functions as a transcriptional co-repressor by physically associating with GATA4, a cardiac-enriched transcriptional activator. We have found that mice with a targeted disruption of the FOG-2 gene die in mid-gestation from cardiac failure secondary to cardiac malformations.  These results demonstrate the importance of FOG-2 in cardiogenesis and suggest that transcriptional repression, in addition to activation, plays a critical role in cardiac development.  Ongoing work in the lab is directed toward characterizing the mechanisms by which FOG genes mediate transcriptional repression and the importance of such pathways for proper cardiac development. 

Selected Papers

Svensson, E. C., Huggins, G. S., Lin, H., Clendenin, C., Jiang, F., Tufts, R., Dardick, F. B., and Leiden, J. M. (2000) "A Syndrome of Tricuspid Atresia in Mice with a Targeted Mutation of the Gene Encoding FOG-2” Nature Genetics 25, 353-356.

Lin, A. C., Roche, A.E., Wilk, J., and Svensson, E.C. (2004) “The N-termini of Friend of GATA (FOG) Proteins Define a Novel Transcriptional Repression Motif and a Superfamily of Transcriptional Repressors” J. Biol. Chem. 279, 55017-55023.

Walton, R.Z., Bruce, A., Olivey, H. E., Najib, K., Johnson, V., Early, J., Ho, R.K. and Svensson, E.C. (2006) “Fog1 is Required for Cardiac Looping in Zebrafish” Dev. Biol. 289, 482-493.

Flagg, A. E., Early, J. U., and Svensson, E. C. (2007) "FOG-2 Attenuates Endothelial-to Mesenchymal Transformation in the Endocardial Cushions of the Developing Heart" Dev. Biol., 304, 308-316.

Dale, R. M., Remo, B. F., and Svensson, E. C. (2007) “An Alternative Transcript of the FOG-2 Gene Encodes a FOG-2 Isoform lacking the FOG Repression Motif” Biochem. Biophys. Res. Commun., 357, 683-687.

Roche, A. E., Bassett, B. J., Samant, S. A., Hong, W., Blobel, G.A., and Svensson, E. C. (2008) “The Zinc Finger and C-terminal Domains of MTA Proteins are Required for FOG-2 Mediated Transcriptional Repression via the NuRD Complex” J. Mol. Cell. Cardiol., 44, 352-360.

McNally, E. M., and Svensson, E. C. (2009) “Setting the Pace:  Tbx3 and Tbx18 in Cardiac Conduction System Development” Circ. Res., 104, 285-287.

Kim, G.K., Samant, S. A., Earley, J. U., and Svensson, E. C. (2009) “Translational Control of FOG-2 Expression in Cardiomyocytes by MicroRNA-130A”, PLOS One, in press.

Svensson, E.C. (2009) “Look Who’s Talking:  FGFs and BMPs in the Proepicardium” Circ. Res., 105, 406-7.