Members of the NK-2 family of homeodomain proteins, which include Nkx-2.2, Nkx-2.5, Nkx-2.6 and Nkx-2.8, are key regulators of growth and development in several tissues, including brain, heart and pancreas. Nkx-2.2 is responsible for directing ventral neuronal patterning in response to graded Shh signaling. 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. 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. Nkx-2.8, also designated NK-2 homolog H, NKX2H or Nkx-2.9, is a nuclear protein that contains one homeobox DNA-binding domain, indicating a possible role in development.