The Nkx2-5 gene, or Nk2 homeobox 5, is involved in the differentiation and commitment of the myocardial lineage; specifically, it is one of the markers of the cardiac mesoderm. It is a mediator of the second heart field development and regulates and many transcription factors and signaling molecules such as Rspo3, Wnt, and its main transcription factor: Nkx2.5.
Nkx2.5 is a transcription factor that activates MEF2, an important regulator in cellular differentiation, and regulates heart development. It is required for myocardial growth and proliferation, the formation of trabeculae (muscular ridges in the ventricles) and the outflow tract.
Nkx2.5 mutants show many irregular heart formations. In some Nkx2.5 mutants, the cardiac tube is formed but the endocardial cushions and trabeculae are absent. There are also signs that Nkx2.5 is not expressed uniformly in the heart because in the event there is a loss of this transcription factor, there are signs of malformation in the right ventricle and outflow track but not in the left ventricle. These defects and mutations can lead to heart looping defects, reduced function of the AV node, congenital heart disease, and atrial septal defects. The knockout model for Nkx2.5 in embryonic mice found that the amount of Nkx2.5’s influence corresponds to the number of myocytes that differentiate into conduction cells. A lack of Nkx2.5 in mice reduced the function of the AV node leading to congenital heart disease which could in turn have an effect on myocardial development and other processes.