XB-ART-8489J Biol Chem November 9, 2001; 276 (45): 42252-8.
Nkx2-5 activity is essential for cardiomyogenesis.
The homeobox transcription factor tinman is essential for heart vessel formation in Drosophila. In contrast, mice lacking the murine homologue Nkx2-5 are defective in cardiac looping but not in cardiac myocyte development. The lack of an essential role for Nkx2-5 in cardiomyogenesis in mammalian systems is most likely the result of genetic redundancy with family members. In this study, we used a dominant negative mutant of Nkx2-5, created by fusing the repressor domain of engrailed 2 to the Nkx2-5 homeodomain, termed Nkx/EnR. Expression of Nkx/EnR inhibited Me(2)SO-induced cardiomyogenesis in P19 cells but not skeletal myogenesis. Nkx/EnR inhibited expression of cardiomyoblast markers, such as GATA-4 and MEF2C, but not of mesoderm markers, such as Brachyury T and Wnt5b, or of skeletal lineage markers, such as MyoD and Mox1. To identify the minimal region of Nkx2-5 that can trigger cardiomyogenesis, we analyzed the activity of various Nkx2-5 deletion mutants. The C-terminal domain was not necessary for the ability of Nkx2-5 to induce cardiomyogenesis and loss of this domain did not enhance myogenesis. Therefore, Nkx2-5 function is essential for commitment of mesoderm into the cardiac muscle lineage, and the N-terminal region, together with the homeodomain, is sufficient for cardiomyogenesis in P19 cells.
PubMed ID: 11526122
Article link: J Biol Chem
Species referenced: Xenopus laevis
Genes referenced: mef2c myod1 nkx2-5 nox1 tbxt wnt5b