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.