T-box factors determine cardiac design.

Heart Failure Research Center, Department of Anatomy and Embryology, Academic Medical Center, Amsterdam, The Netherlands.
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.81). 04/2007; 64(6):646-60.
Source: PubMed


The heart of higher vertebrates is a structurally complicated multi-chambered pump that contracts synchronously. For its proper function a number of distinct integrated components have to be generated, including force-generating compartments, unidirectional valves, septa and a system in charge of the initiation and coordinated propagation of the depolarizing impulse over the heart. Not surprisingly, a large number of regulating factors are involved in these processes that act in complex and intertwined pathways to regulate the activity of target genes responsible for morphogenesis and function. The finding that mutations in T-box transcription factor-encoding genes in humans lead to congenital heart defects has focused attention on the importance of this family of regulators in heart development. Functional and genetic analyses in a variety of divergent species has demonstrated the critical roles of multiple T-box factor gene family members, including Tbx11, -2, -3, -5, -18 and -20, in the patterning, recruitment, specification, differentiation and growth processes underlying formation and integration of the heart components. Insight into the roles of T-box factors in these processes will enhance our understanding of heart formation and the underlying molecular regulatory pathways.

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    • "This suggests that chamber formation should be repressed regionally and, consequently, that maintenance of primary myocardium is crucial for the localized formation of the chamber. Two closely related transcription factors of the T-box gene family, Tbx2 and Tbx3, are involved in this repression [75] [76] [77] [78]. "
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    • "Both of these elements will define the ultimate transcriptional function of the factor and hence its downstream gene targets. The T-box factors Tbx2, Tbx3 and Tbx5 are known, for instance, to bind the homeobox protein Nkx2.5 [13, 17–19]. Since T-box factors are expressed and are required for the development of many different organs and tissues, complex forming with a factor such as Nkx2.5, which has a more cardiac-restricted expression pattern, may be instrumental in determining a set of heart specific T-box target genes. "
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