John D. Mably

Department of Genetics, HMS

Department of Pediatrics, Cardiovascular Research
Children's Hospital Boston
Enders 1261.1
320 Longwood Avenue
Boston, MA 02115
Tel: (617) 919-4758
Fax: (617) 731-0787
Email: john.mably@childrens.harvard.edu

Web Page: The Mably Lab Page
2 technicians

Cardiovascular Research at Childrens Hospital Boston

The focus of my research is the characterization of zebrafish mutations that affect cardiac development. This work currently centers on the study of three zebrafish mutants collectively referred to as the "big hearts" (valentine, heart of glass,santa). The hearts are huge, but thin-walled because the myocardium does not thicken as in the normal heart. The number of cells is not altered, implicating a defect in the concentric growth of the myocardium in these mutants. They have endocardium, but do not develop endocardial cushions, which give rise to valves.

The genes responsible for these mutations have been identified and we are currently looking at the relationship between these newly defined genes and the phenotype of the mutants. The similarity between the phenotypes of the three big hearts suggests the intriguing possibility of a common pathway. We can increase (by RNA injection) or decrease (by antisense morpholino oligomer injection) expression of these genes in the zebrafish, and together with biochemical approaches we hope to define the interactions between them.

Two of these three genes have never been described previously, and none of the three have been examined in the context of cardiac development. In addition, the development of the zebrafish heart is very similar to that of the early mammalian embryo so that any insights provided by this work will be extendable to human studies with relevance for human cardiac disease.

References:

• Mably, JD, Chuang, LP, Serluca, FC, Mohideen, M-APK, Chen, J-N, and Fishman, MC.  santa and valentine Pattern Myocardiac Growth and Vessel Formation in the Zebrafish.  2006, Development;133:3139-3146.
• Chen, J-N, Cowan, DB, and Mably, JD (2005). Cardiogenesis and the Regulation of Cardiac-Specific Gene Expression. Heart Failure Clinics; 1:157-170.
• Mably, JD, Mohideen, M-APK, Burns, CG, Chen, J-N, and Fishman, MC.  heart of glass regulates the concentric growth of the heart in zebrafish.  Curr Biol 2003;13:2138-2147.