Biomedical Sciences Graduate Program | University of California, San Francisco

Benoit Bruneau, PhD
Transcriptional regulation of heart development

Selected Publications | Complete Publications

phone	(415) 734-2708
email	bbruneau@gladstone.ucsf.edu
additional websites	Lab Website
secondary research affiliation	Vascular & Cardiac Biology

The main focus of our lab is to understand how a heart becomes a heart: what cell lineage decisions take place to direct cardiac differentiation, and what morphogenetic and patterning processes occur to assemble all of the heart's components into a functional organ. In both cases, we are primarily interested in regulation by transcription factors and chromatin remodeling. This encompasses both early development and differentiation, as well as postnatal physiology.

Why study heart development? We believe that primary defects in patterning in early heart development are at the root of congenital heart defects, which affect approximately 1% of live-born children, and we want to understand how these defects occur, to perhaps be able to uncover new and improved diagnostic or even therapeutic options. Also, by understanding how cardiac lineage specification occurs, we can better design stem cell-based interventions of cardiac repair, based on the knowledge of what drives an uncommitted cell towards a specific cardiac fate.

The family of genes we study the most are the T-box and Iroquois transcription factors. These transcription factors are involved in important patterning and morphogenetic decisions at various stages of heart development. We have also recently begun a foray into cardiac chromatin remodeling and modification factors, enzymes that unwind DNA or modify histones to turn genes on or off. We are particularly interested in how these factors control cardiac cell lineage decisions. These chromatin remodeling factors may also be key to pushing a stem cell into becoming a heart cell, perhaps opening up new avenues for cardiac regenerative medicine.

Selected Publications

*Indicates graduate students (present or past)

Lickert H., Takeuchi J.K., von Both I., Walls J., McAuliffe F., Adamson S.L., Henkelman R.M., Wrana J.L., Rossant J., & Bruneau B.G. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 2004; 432:107–112

Costantini D.L., Arruda E.P., Agarwal P., Kim K.-H., Zhu Y., Zhu W., Lebel M., Cheng C.W., Park C.Y., Pierce S., Guerchicoff A., Pollevick G., Chan T.Y., Kabir M.G., Cheng S.H., Husain M., Antzelevitch C., Srivastava D.,Gross G.J., Hui C.-c., Backx P.H., & Bruneau B.G. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell 2005; 123:347–358

Koshiba-Takeuchi K., Takeuchi J.K., Arruda E.P., Kathiriya I.S., Mo R., Hui C.-c., Srivastava D., & Bruneau B.G. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nature Genetics 2006;38:175–183

Takeuchi J.K., Lickert H., Bisgrove B., Sun, X., Yamamoto M., Chawengsaksophak K., Hamada H., Yost H.J., Rossant J., & Bruneau B.G. Baf60c is a nuclear Notch signalling component required for the establishment of left-right asymmetry. Proc. Natl. Acad. Sci. USA 2007; 846–851

Bruneau B.G. The developmental genetics of congenital heart disease. Nature 2008; 451:943–948

Takeuchi J.K., & Bruneau B.G. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature, 2009 459:708-711

information last updated August 2009