Abstract
The heart is a primary source of epinephrine and norepinephrine during embryonic development, yet little is known about the cardiac cells that produce these catecholamine hormones. To identify when and where catecholamine-synthesizing cells are found in the embryonic heart, we developed a novel mouse genetic model by "knocking-in" the Cre-recombinase gene to the locus encoding for the epinephrine biosynthetic enzyme, phenylethanolamine n-methyltransferase. When crossed with ROSA26 reporter mice, the beta-galactosidase gene is activated in adrenergic cells. A major advantage of this approach is that it allows detection of adrenergic cells and their progeny, regardless of whether the progeny cells retain an adrenergic phenotype or not. Our data show that adrenergic cells appear as early as embryonic day 8.5 and continue to accumulate in substantial numbers through birth in the mouse heart, where they appear to share common ancestry with myocardial lineages. Large numbers of atrial and especially ventricular myocytes appear to be derived from embryonic adrenergic cells in the heart. In addition, many of the pacemaking cells in the sinoatrial and atrioventricular nodes also appear to be derived from an adrenergic lineage. Thus, our results suggest that catecholamine-synthesizing cells serve as cardiomyocyte progenitors in the embryonic heart.