Detailed lines of work > Vertebrate heart development

  • Figure 1: Rightward looping of the heart tube in the chick embryo. Adapted from Izpisua Belmonte, Sci. Am. 280:46-51; 1999.

  • Figure 2: Regulation of heart tube fusion by non-canonical Wnt signaling. Effects of a dominant-negative version of Dishevelled (Dvl DEP) on zebrafish heart development. Transgenic zebrafish embryos carrying mlc2a-eGFP reporter were injected with Control AP mRNA (H) or Dvl DEP mRNA (I, J) and allowed to grow for 48 h. Injection of Dvl DEP even in low concentrations (J) led to the formation of two laterally positioned hearts (cardia bifida) in zebrafish embryos. Ventral views, anterior to the top. From Matsui et al, Genes & Dev 19:164-175; 2005.

  • Video 1: Heart formation during zebrafish embryo development

The heart is a highly modified tube that functions as a pump to drive blood circulation to the body in all vertebrates and, in animals with lungs, also to the pulmonary system. Proper heart function is not only essential for the life of vertebrate animals, but also for the development of vertebrate embryos. As such, the heart is first organ that forms during vertebrate embryogenesis.

At the tissue level, the heart is a complex structure that comprises many different cell types with highly specialized functions. As an organ, the heart is formed after complex processes including cell polarization and migration, fusion of cell fields and tube formation, and tube looping. Errors in these processes result in congenital heart malformations, which represent a major fraction of developmental anomalies of clinical significance. During adulthood, functional and/or structural alterations of otherwise normally formed hearts cause a complex spectrum of cardiovascular diseases, a leading cause of health-related problems in developed countries.

Our laboratory is interested in understanding the molecular and cellular mechanisms that regulate various aspects of heart development in vertebrates. For this purpose, we combine genetic manipulation and in vivo analyses of chick, mouse, and zebrafish embryos and in vitro experiments using mouse and human embryonic stem cells.

We exploit the relative experimental advantages of these different models to address basic questions as to the molecular mechanisms of myocardial fate specification and differentiation. Modern techniques of in vivo imaging of developing embryos allow us to directly examine specific behaviors at the cellular and tissue levels associated with different aspects of heart patterning. The zebrafish is particularly helpful in this respect, for embryo development occurs independently of proper heart function for extended periods of time. A large-scale sensitized mutagenesis screen has been conducted in our laboratory to identify novel genes required for heart development in the zebrafish. Several mutants are currently being analyzed in detail.

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