Molecular and cellular mechanisms of second heart field development in zebrafish.

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A fundamental question in biology is how organs develop and assume their mature, adult form. This is especially true for the heart, which must continue to maintain blood flow in the developing embryo while growing and developing. A surprising finding has been that much of heart development occurs by addition of cells to the already beating heart tube. A group of cells termed the "secondary heart field" (SHF) migrates into the heart and forms a large portion of the mature heart, including the right ventricle, outflow tract, much of the atria and septa that separate the 4 chambers. SHF addition occurs in mice, the model typically used to study heart development, at at time when the embryo is developing in the uterus, making detailed observation of this key process very difficult. Due to its optical clarity, rapid external development and amenability to genetic approaches, the zebrafish has become a powerful tool to study how heart development. My group has recently found that development of the zebrafish heart also involves addition of a SHF-like population of cells. As heart development can be visualized in real-time in the zebrafish embryo, we are now positioned to examine the SHF in a way not possible in the mouse model used to date. The experiments outlined in this proposal aim to discover the cellular and molecular mechanisms responsible for SHF development using the many advantages of the zebrafish embryo. Specifically, we will study in real time at the cellular level how SHF cells are added to the developing heart. We will additionally isolate SHF cells at key time points in their development and identify genes that play essential roles in SHF biology. We will therefore be able to examine critical, yet until now impossible to study, aspects of heart development that can only be visualized in a static fashion in other model systems such as the mouse. This will allow us to define key regulators of SHF development and growth of the heart.