Elevated expression of Nkx-2.5 in developing myocardial conduction cells

Citation
Ps. Thomas et al., Elevated expression of Nkx-2.5 in developing myocardial conduction cells, ANAT REC, 263(3), 2001, pp. 307-313
Citations number
40
Categorie Soggetti
Experimental Biology
Journal title
ANATOMICAL RECORD
ISSN journal
0003276X → ACNP
Volume
263
Issue
3
Year of publication
2001
Pages
307 - 313
Database
ISI
SICI code
0003-276X(20010701)263:3<307:EEONID>2.0.ZU;2-C
Abstract
A number of different phenotypes emerge from the mesoderm-derived cardiomyo genic cells of the embryonic tubular heart, including those comprising the cardiac conduction system. The transcriptional regulation of this phenotypi c divergence within the cardiomyogenic lineage remains poorly characterized . A relationship between expression of the transcription factor Nkx-2.5 and patterning to form cardiogenic mesoderm subsequent to gastrulation is well established. Nkx-2.5 mRNA continues to be expressed in myocardium beyond t he looped, tubular heart stage. To investigate the role of Nkx-2.5 in later development, we have determined the expression pattern of Nkx-2.5 mRNA by in situ hybridization in embryonic chick, fetal mouse, and human hearts, an d of Nkx-2.5 protein by immunolocalization in the embryonic chick heart. As development progresses, significant nonuniformities emerge in Nkx-2.5 expr ession levels. Relative to surrounding force-generating ("working") myocard ium, elevated Nkx-2.5 mRNA signal becomes apparent in the specialized cells of the conduction system. Similar differences are found in developing chic k, human, and mouse fetal hearts, and nuclear-localized Nkx-2.5 protein is prominently expressed in differentiating chick conduction cells relative to adjacent working myocytes. This tissue-restricted expression of Nkx-2.5 is transient and correlates with the timing of spatio-temporal recruitment of cells to the central and the peripheral conduction system. Our data repres ent the first report of a transcription factor showing a stage-dependent re striction to different parts of the developing conduction system, and sugge st some commonality in this development between birds and mammals. This dyn amic pattern of expression is consistent with the hypothesis that Nkx-2.5, and its level of expression, have a role in regulation and/or maintenance o f specialized fate selection by embryonic myocardial cells. Anat Rec 263:30 7-313, 2001. (C) 2001 Wiley-Liss, Inc.