Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is expressed in the developing dorsal vessel and in the equivalent of the vertebrate heart. Mutations in tinman result in loss of heart formation in the embryo, suggesting that tinman is essential for Drosophila heart formation. Furthermore, abundant expression of Csx, the presumptive mouse homolog of tinman, is observed only in the heart from the time of cardiac differentiation. CSX, the human homolog of murine Csx, has a homeodomain sequence identical to that of Csx and is expressed only in the heart, again suggesting that CSX plays an important role in human heart formation.[supplied by OMIM]
Recently, postnatal roles of cardiac transcription factors have been extensively investigated. Consistent with the direct transactivation of numerous cardiac genes reactivated in response to hypertrophic stimulation, cardiac transcription factors are profoundly involved in the generation of cardiac hypertrophy or in cardioprotection from cytotoxic stress in the adult heart. Nkx-2.5 transcription factor may help myocytes endure cytotoxic stress, even though further exploration in this field is required.
NKX2-5 has been shown to interact with GATA4 and TBX5. NKX 2.5 is a transcription factor that regulates heart development in humans. NKX2.5 works along with MEF2, HAND1, and HAND2 transcription factors to direct heart looping during early heart development. NKX2.5 in vertebrates is equivalent to the ‘tinman’ gene in Drosophila and directly activates the MEF2 gene to control cardiomyocyte differentiation. NKX2.5 operates in a positive feedback loop with GATA transcription factors to regulate cardiomyocyte formation. NKX2.5 influences HAND1 and HAND2 transcription factors that control the essential asymmetrical development of the heart’s ventricles. Gene mutations of NKX2.5 lead to heart looping defects, conduction defects, and atrial septal defects in the developing heart.
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