Fundamental regulation of chordate heart development
Principal Investigator: Bradley Davidson
Abstract: This research proposal focuses on elucidating heart developmental genetics in the primitive chordate Ciona intestinalis. Initial efforts will focus on the regulation and function of the single Ciona ortholog to the vertebrate Nkx 2.x gene family, Ci-Nkx. The ability to test reporter constructs through electroporation will allow rapid identification of the regulatory elements which control Ci-Nkx expression. This technique will also permit prompt identification of functionally important binding sites within these elements. Identification of functional binding sites will be employed to identify factors which regulate Nkx. Misexpression and repression of Ci-Nkx will be employed to determine its functional significance and to identify downstream target genes. Research on Nkx 2.5 in vertebrate heart development has been hindered by the presence of numerous paralogs. Therefore, analysis of Ciona Nkx regulation and function can make a significant contribution towards understanding conserved aspects of vertebrate heart genetics. A fundamental understanding of heart genetics is essential to the development of medical treatments for heart-related diseases and birth defects.
Funding Period: 2003-07-01 - 2006-06-30
more information: NIH RePORT
- Uncoupling heart cell specification and migration in the simple chordate Ciona intestinalisBrad Davidson
Department of Molecular and Cellular Biology, Division of Genetics and Development, University of California, Berkeley, CA 94720, USA
Development 132:4811-8. 2005..We discuss the implications of Tbx6-Mesp interactions for the evolution of cardiac mesoderm in invertebrates and vertebrates...
- Ciona intestinalis as a model for cardiac developmentBrad Davidson
Department of Molecular and Cellular Biology, Division of Genetics and Development, University of California, Berkeley, CA 94720, United States
Semin Cell Dev Biol 18:16-26. 2007..I also discuss the potential of employing Ciona to decipher a comprehensive chordate gene network and to determine how this network controls heart morphogenesis...