Elevated expression of Nkx‐2.5 in developing myocardial conduction cells

PS Thomas, H Kasahara, AM Edmonson… - … Record: An Official …, 2001 - Wiley Online Library
PS Thomas, H Kasahara, AM Edmonson, S Izumo, MH Yacoub, PJR Barton, RG Gourdie
The Anatomical Record: An Official Publication of the American …, 2001Wiley Online Library
A number of different phenotypes emerge from the mesoderm‐derived cardiomyogenic cells
of the embryonic tubular heart, including those comprising the cardiac conduction system.
The transcriptional regulation of this phenotypic 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 the …
Abstract
A number of different phenotypes emerge from the mesoderm‐derived cardiomyogenic cells of the embryonic tubular heart, including those comprising the cardiac conduction system. The transcriptional regulation of this phenotypic 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 the 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, and of Nkx‐2.5 protein by immunolocalization in the embryonic chick heart. As development progresses, significant nonuniformities emerge in Nkx‐2.5 expression levels. Relative to surrounding force‐generating (“working”) myocardium, elevated Nkx‐2.5 mRNA signal becomes apparent in the specialized cells of the conduction system. Similar differences are found in developing chick, 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 represent the first report of a transcription factor showing a stage‐dependent restriction to different parts of the developing conduction system, and suggest some commonality in this development between birds and mammals. This dynamic 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 of specialized fate selection by embryonic myocardial cells. Anat Rec 263:307–313, 2001. © 2001 Wiley‐Liss, Inc.
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