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

The cellular localization of transforming growth factor-alpha (TGFalpha) mRNA in juvenile and adult rat forebrain was examined using in situ hybridization with a S-35-labeled cRNA probe. TGFalpha cRNA-labeled neuronal perikarya were distributed across many forebrain regions including the olfactory bulb, caudate-putamen, nucleus accumbens, olfactory tubercle, ventral pallidum, amygdala, hippocampal stratum granulosum and CA3 stratum pyramidale, and piriform, entorhinal, and retrosplenial cortices. TGFalpha cRNA-hybridizing cells were also localized to several thalamic nuclei and to the suprachiasmatic, dorsomedial, and ventromedial nuclei of the hypothalamus. In addition, labeled cells were present in regions of white matter including the corpus callosum, anterior commissure, internal and external capsules, optic tract, and lateral olfactory tract. Thus, both neurons and glia appear to synthesize TGFalpha in normal brain. Hybridization densities were greater in neuronal fields at 2 weeks of age compared with the adult, suggesting a role for TGFalpha in the development of several forebrain systems. Our results demonstrating the prominent and wide-spread expression of TGFalpha mRNA in forebrain, combined with the extremely low abundance of epidermal growth factor mRNA in brain, support the argument that TGFalpha is the principal endogenous ligand for the epidermal growth factor receptor in normal brain.