CELLULAR-LOCALIZATION OF TRANSFORMING GROWTH FACTOR-ALPHA MESSENGER-RNA IN RAT FOREBRAIN

The cellular localization of transforming growth factor-alpha (TGFalph a) mRNA in juvenile and adult rat forebrain was examined using in situ hybridization with a S-35-labeled cRNA probe. TGFalpha cRNA-labeled n euronal perikarya were distributed across many forebrain regions inclu ding the olfactory bulb, caudate-putamen, nucleus accumbens, olfactory tubercle, ventral pallidum, amygdala, hippocampal stratum granulosum and CA3 stratum pyramidale, and piriform, entorhinal, and retrosplenia l cortices. TGFalpha cRNA-hybridizing cells were also localized to sev eral thalamic nuclei and to the suprachiasmatic, dorsomedial, and vent romedial nuclei of the hypothalamus. In addition, labeled cells were p resent in regions of white matter including the corpus callosum, anter ior commissure, internal and external capsules, optic tract, and later al olfactory tract. Thus, both neurons and glia appear to synthesize T GFalpha in normal brain. Hybridization densities were greater in neuro nal fields at 2 weeks of age compared with the adult, suggesting a rol e for TGFalpha in the development of several forebrain systems. Our re sults demonstrating the prominent and wide-spread expression of TGFalp ha mRNA in forebrain, combined with the extremely low abundance of epi dermal growth factor mRNA in brain, support the argument that TGFalpha is the principal endogenous ligand for the epidermal growth factor re ceptor in normal brain.