NKX-2.5 - A NOVEL MURINE HOMEOBOX GENE EXPRESSED IN EARLY HEART PROGENITOR CELLS AND THEIR MYOGENIC DESCENDANTS

We have isolated two murine homeobox genes, Nkx-2.5 and Nkx-2.6, that are new members of a sp sub-family of homeobox genes related to Drosop hila NK2, NK3 and NK4/msh-2. In this paper, we focus on the Nkx-2.5 ge ne and its expression pattern during post-implantation development. Nk x-2.5 transcripts are first detected at early headfold stages in myoca rdiogenic progenitor cells. Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, foetal and adult hearts. Transcripts are also detected in future pharyngeal e ndoderm, the tissue believed to produce the heart inducer. Expression in endoderm is only found laterally, where it is in direct apposition to promyocardium, suggesting an interaction between the two tissues. A fter foregut closure, Nkx-2.5 expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid pr imordium, a derivative of the pharyngeal floor, continues to express N kx-2.5 after transcript levels diminish in the rest of the pharynx. Nk x-2.5 transcripts are also detected in lingual muscle, spleen and stom ach. The expression data implicate Nkx-2.5 in commitment to and/or dif ferentiation of the myocardial lineage. The data further demonstrate t hat cardiogenic progenitors can be distinguished at a molecular level by late gastrulation. Nkx-2.5 expression will therefore be a valuable marker in the analysis of mesoderm development and an early entry poin t for dissection of the molecular basis of myogenesis in the heart.