Development, Vol 119, Issue 2 419-431, Copyright © 1993 by Company of Biologists

JOURNAL ARTICLES

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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				T. Clark, S. Conway, I. Scott, P. Labosky, G Winnier, J Bundy, B. Hogan, and D. Greenspan The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart Development, January 6, 1999; 126(12): 2631 - 2642. [Abstract] [PDF]

				J Xavier-Neto, C. Neville, M. Shapiro, L Houghton, G. Wang, W Nikovits, F. Stockdale, and N Rosenthal A retinoic acid-inducible transgenic marker of sino-atrial development in the mouse heart Development, January 6, 1999; 126(12): 2677 - 2687. [Abstract] [PDF]

				M Tanaka, S. Wechsler, I. Lee, N Yamasaki, J. Lawitts, and S Izumo Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5 Development, January 4, 1999; 126(7): 1439 - 1450. [Abstract] [PDF]

				H Chang, D Huylebroeck, K Verschueren, Q Guo, M. Matzuk, and A Zwijsen Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects Development, January 4, 1999; 126(8): 1631 - 1642. [Abstract] [PDF]

				M. Horb and G. Thomsen Tbx5 is essential for heart development Development, January 4, 1999; 126(8): 1739 - 1751. [Abstract] [PDF]

				M Tanaka, Z Chen, S Bartunkova, N Yamasaki, and S Izumo The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development Development, January 3, 1999; 126(6): 1269 - 1280. [Abstract] [PDF]

				C Xu, G Liguori, M. Persico, and E. Adamson Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes Development, January 2, 1999; 126(3): 483 - 494. [Abstract] [PDF]

				J. Reecy, X Li, M Yamada, F. DeMayo, C. Newman, R. Harvey, and R. Schwartz Identification of upstream regulatory regions in the heart-expressed homeobox gene Nkx2-5 Development, January 2, 1999; 126(4): 839 - 849. [Abstract] [PDF]

				H. Kasahara and S. Izumo Identification of the In Vivo Casein Kinase II Phosphorylation Site within the Homeodomain of the Cardiac Tisue-Specifying Homeobox Gene Product Csx/Nkx2.5 Mol. Cell. Biol., January 1, 1999; 19(1): 526 - 536. [Abstract] [Full Text] [PDF]

				C. Lien, C Wu, B Mercer, R Webb, J. Richardson, and E. Olson Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer Development, January 1, 1999; 126(1): 75 - 84. [Abstract] [PDF]

				I. S. Skerjanc, H. Petropoulos, A. G. Ridgeway, and S. Wilton Myocyte Enhancer Factor 2C and Nkx2-5 Up-regulate Each Other's Expression and Initiate Cardiomyogenesis in P19 Cells J. Biol. Chem., December 25, 1998; 273(52): 34904 - 34910. [Abstract] [Full Text] [PDF]

				Y. Lee, T. Shioi, H. Kasahara, S. M. Jobe, R. J. Wiese, B. E. Markham, and S. Izumo The Cardiac Tissue-Restricted Homeobox Protein Csx/Nkx2.5 Physically Associates with the Zinc Finger Protein GATA4 and Cooperatively Activates Atrial Natriuretic Factor Gene Expression Mol. Cell. Biol., June 1, 1998; 18(6): 3120 - 3129. [Abstract] [Full Text]

				J. L. Sepulveda, N. Belaguli, V. Nigam, C.-Y. Chen, M. Nemer, and R. J. Schwartz GATA-4 and Nkx-2.5 Coactivate Nkx-2 DNA Binding Targets: Role for Regulating Early Cardiac Gene Expression Mol. Cell. Biol., June 1, 1998; 18(6): 3405 - 3415. [Abstract] [Full Text]

				W. Shawlot, J. M. Deng, and R. R. Behringer Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior neural induction and somitogenesis PNAS, May 26, 1998; 95(11): 6198 - 6203. [Abstract] [Full Text] [PDF]

				H. Kasahara, S. Bartunkova, M. Schinke, M. Tanaka, and S. Izumo Cardiac and Extracardiac Expression of Csx/Nkx2.5 Homeodomain Protein Circ. Res., May 19, 1998; 82(9): 936 - 946. [Abstract] [Full Text] [PDF]

				J. T. Thompson, M. S. Rackley, and T. X. O'Brien Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1569 - H1573. [Abstract] [Full Text] [PDF]

				C. Haun, J. Alexander, D. Y. Stainier, and P. G. Okkema Rescue of Caenorhabditis elegans pharyngeal development by a vertebrate heart specification gene PNAS, April 28, 1998; 95(9): 5072 - 5075. [Abstract] [Full Text] [PDF]

				H. Oguchi and S. Kimura Multiple Transcripts Encoded by the Thyroid-Specific Enhancer-Binding Protein (T/EBP)/Thyroid-Specific Transcription Factor-1 (TTF-1) Gene: Evidence of Autoregulation Endocrinology, April 1, 1998; 139(4): 1999 - 2006. [Abstract] [Full Text] [PDF]