The roles of FoxH1 and TGFbeta signaling in directing asymmetric cardiac morphogenesis

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How cells are arranged in three dimensions to produce functional organs such as the heart is a fundamental question in biology that has not been fully addressed. Once cells are instructed to become heart tissue, they must coordinate their movements to organize into a multi-layered functional structure. One critical aspect of this process is how cells arrange differently on the left versus the right side of the heart, commonly referred to as left-right patterning. Previous work has determined that the FoxH1 transcription factor plays an important role in integrating multiple TGFbeta signals in heart cells so that they respond appropriately to left-right patterning information. Utilizing the powerful genetics available in the zebrafish system, the roles of FoxH1 in coordinating TGFbeta signaling and directing left-right cell migrations in the developing heart will be explored. The outcome of this work will be a better understanding of how the heart forms, especially with regards to left-right patterning. This information will have significant impact on stem cell studies aimed at producing functional organs for transplant. This project is well suited to be conducted by graduate students and undergraduates and will be the framework for recruiting women and underrepresented minorities into research through thesis work at Princeton and through the Summer Research Experience program conducted by the Department of Molecular Biology.