T-box genes are transcription factors which play fundamental roles in key developmental processes of lineage determination and morphogenesis. A number of t-box genes are expressed in the developing cardiovascular system. Mutations in several human t-box genes have been shown to cause congenital cardiovascular disease. Tbx20 is a recently described member of this family which is expressed at high levels in early cardiac primordia in both invertabrates and vertabrates. Tbx20 is also expressed in adult atria and at high levels in the sino-atrial node. From these observations, our hypothesis is that tbx20 plays a critical role at distinct stages of heart development and in adult heart. To date, nothing is known as to the function of tbx20 in the heart. The proposed studies will perform gain of function and loss of function experiments in developing, differentiating, and adult heart to examine the role of tbx20 in heart at these distinct developmental timepoints. Comprehensive analyses will be carried out at the morphological, hostological, and functional levels. Our studies will be performed utilizing both Xenopus laevis and mouse, capitalizing on the strengths of each system.
Our specific aims are: 1) To investigate the initial role of tbx20 in heart development by loss of function and gain of function experiments in Xenopus laevis embryo. 2) To investigate the role of tbx20 in cardiac primordia and differentiating heart by loss of function and gain of function experiments in stably transgenic Xenopus laevis embryo. 3) To investigate the role of tbx20 in cardiogenesis and in the adult heart, by generation or floxed allele of tbx20 in mice.
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