Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants

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Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants

TJ Lints, LM Parsons, L Hartley, I Lyons and RP Harvey
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

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 Drosophila NK2, NK3 and NK4/msh-2. In this paper, we focus on the Nkx-2.5 gene and its expression pattern during post-implantation development. Nkx-2.5 transcripts are first detected at early headfold stages in myocardiogenic 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 endoderm, 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. After foregut closure, Nkx-2.5 expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium, a derivative of the pharyngeal floor, continues to express Nkx-2.5 after transcript levels diminish in the rest of the pharynx. Nkx-2.5 transcripts are also detected in lingual muscle, spleen and stomach. The expression data implicate Nkx-2.5 in commitment to and/or differentiation of the myocardial lineage. The data further demonstrate that 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 point for dissection of the molecular basis of myogenesis in the heart.

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				C. A. Risebro, N. Smart, L. Dupays, R. Breckenridge, T. J. Mohun, and P. R. Riley Hand1 regulates cardiomyocyte proliferation versus differentiation in the developing heart Development, November 15, 2006; 133(22): 4595 - 4606. [Abstract] [Full Text] [PDF]

				E. E. Creemers, L. B. Sutherland, J. McAnally, J. A. Richardson, and E. N. Olson Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development Development, November 1, 2006; 133(21): 4245 - 4256. [Abstract] [Full Text] [PDF]

				C. Karamboulas, A. Swedani, C. Ward, A. S. Al-Madhoun, S. Wilton, S. Boisvenue, A. G. Ridgeway, and I. S. Skerjanc HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage J. Cell Sci., October 15, 2006; 119(20): 4305 - 4314. [Abstract] [Full Text] [PDF]

				B. Ding, C.-j. Liu, Y. Huang, R. P. Hickey, J. Yu, W. Kong, and P. Lengyel p204 Is Required for the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes: ITS EXPRESSION IS ACTIVATED BY THE CARDIAC GATA4, NKX2.5, AND TBX5 PROTEINS J. Biol. Chem., May 26, 2006; 281(21): 14882 - 14892. [Abstract] [Full Text] [PDF]

				S. Willey, A. Ayuso-Sacido, H. Zhang, S. T. Fraser, K. E. Sahr, M. J. Adlam, M. Kyba, G. Q. Daley, G. Keller, and M. H. Baron Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor Blood, April 15, 2006; 107(8): 3122 - 3130. [Abstract] [Full Text] [PDF]

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				X. Chi, P. K. Chatterjee, W. Wilson III, S.-X. Zhang, F. J. DeMayo, and R. J. Schwartz Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules PNAS, September 20, 2005; 102(38): 13490 - 13495. [Abstract] [Full Text] [PDF]

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				J. Lynch, L. Guo, P. Gelebart, K. Chilibeck, J. Xu, J. D. Molkentin, L. B. Agellon, and M. Michalak Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca2+-dependent signaling cascade J. Cell Biol., July 4, 2005; 170(1): 37 - 47. [Abstract] [Full Text] [PDF]

				M. K. Singh, V. M. Christoffels, J. M. Dias, M.-O. Trowe, M. Petry, K. Schuster-Gossler, A. Burger, J. Ericson, and A. Kispert Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2 Development, June 15, 2005; 132(12): 2697 - 2707. [Abstract] [Full Text] [PDF]

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