COORDINATE TGF-BETA RECEPTOR GENE-EXPRESSION DURING RAT-HEART DEVELOPMENT

Transforming growth factor-beta (TGF-beta) has been implicated to part icipate in heart development. The receptors which transduce the signal (s) mediated by TGF-beta ligand binding have only recently been cloned . One of the most prominent effects of TGF-beta is inhibition of cell proliferation, a process that is tightly regulated during heart develo pment. Using the developing rat ventricle as a model system, we have d etermined the steady state expression patterns for the Type I, II, and III TGF-beta receptors (TGF-beta Rs). Using RNA isolated from ventric ular chambers on day 18 of gestation through the ninth postnatal week of age, we detected a modest increase in expression levels for Type I and Type III TGF-beta Rs. In contrast, steady state transcript levels for the Type II TGF-beta R showed a profound developmental increase fr om nearly undetectable levels at the fetal ages examined to high level s during the first postnatal week of age. Immunoelectron microscopic l ocalization of Type II TGF-beta R confirmed that the 3-week-old ventri cular myocyte, as well as nonmyocytes, contained immunoreactive materi al. Immunoreactivity was found at both the cell surface as well as int racellular compartment. Regional variations (right ventricle, left ven tricle, or septum) in the expression pattern of several markers of hea rt development, but not the TGP-beta R's, were found in RNA obtained f rom 3-week-old postnatal animals. These data suggest that ''downstream '' effecters of TGF-beta-mediated stimulation are modulated in a devel opmental, regional-specific manner in the neonatal/mature myocardium b y the level of bioactive TGF-beta.