Members of the NK-2 family of homeodomain proteins are key regulators of growth and development in several tissues, including brain, heart and pancreas.Nkx-2.5, also designated cardiac specific homeobox protein (Csx), is a homolog of the Drosophila tinman protein and is essential for normal cardiovascular development. Expression of Nkx-2.5 during cardiomyogenesis is required for cardiac septation, in which a single atrium and ventricle are separated into four chambers. Nkx-2.5 binds to DNA as a monomer, a homodimer or as a heterodimer with Nkx-2.3 or Nkx-2.6, which suggests that the specific protein-protein interactions of Nkx-2.5 are involved in its transcriptional regulatory function. Nkx-2.6, also a homolog of the Drosophila tinman protein, is expressed in the caudal pharyngeal pouches,the caudal heart progenitors, the sinus venosus, the outflow tract of the heart and in a short segment of the gut between stages E8.5 and E10.5 of embryogenesis. Expression of Nkx-2.6 overlaps with that of Nkx-2.5 in the pharynx and heart. However, Nkx-2.6 mutant mice are viable and fertile, which suggests that Nkx-2.6 plays a compensatory function to Nkx-2.5.
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