Neuregulins are a family of growth factors that have been shown to promote
the growth or differentiation of various cell. types. Recently, targeted mu
tations of the genes for neuregulins or their putative receptors by homolog
ous recombination resulted in embryonic lethality characterized by cardiac
malformation. Here we investigate a role for neuregulin in the growth of cu
ltured chick heart cells. Neuregulin induced the tyrosine phosphorylation o
f a 185-kDa protein in cultured heart cells, and it also stimulated an incr
ease in [H-3]thymidine incorporation and BrDU labeling in the cell cultures
. Immunocytochemistry revealed that the increased DNA synthesis was primari
ly in mesenchymal cells and not detected in myocytes or endocardial cells.
These data suggest that neuregulin may function as a paracrine signal in me
senchymal-endothelial interactions during cardiac development. (C) 1999 Aca
demic Press.