DISTINCT LOCALIZATION OF 2 SERINE-THREONINE KINASE RECEPTORS FOR ACTIVIN AND TGF-BETA IN THE RAT-BRAIN AND DOWN-REGULATION OF TYPE-I ACTIVIN RECEPTOR DURING PERIPHERAL-NERVE REGENERATION

The localizations of serine-threonine kinase receptor mRNA for the nov el type I TGF-beta and/or activin receptor named B1 (rat), ALK-4 (mous e) or ActR-IB (human) were demonstrated by in situ hybridization. As t he putative ligand for this receptor in the brain has not yet been cle arly determined, we compared its localization to type II activin recep tor (ActR-II) which is the counterpart of the type I activin receptor. B1 mRNA was widely observed in neuronal cells throughout the brain, a nd especially strong positive signals were found in the cerebral corte x, olfactory tubercle, and hippocampus. The localization of B1 mRNA co incided well with that of ActR-II. This strongly suggests that B1 (ALK -4/ActR-IB) could be the type I activin receptor, as type I and type I I activin receptor were supposed to form a receptor complex. In additi on, we examined the localization of type II TGF-beta receptor (T beta RII) mRNA which is an essential counterpart of the type I TGF-beta rec eptors for TGF-beta signaling. T beta RII mRNA was expressed mainly in non-neuronal cells such as choroid plexus. In addition, T beta RII mR NA expression was also found in a minor population of neuronal cells. T beta RII mRNA-positive neurons were observed in the reticular thalam us, laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and the ventral tegmental nucleus. The localization of T beta RII was markedly different from that of activin receptors in the rat brain. S ince TGF-Ps and activins are known as growth factors and/or survival f actors, we examined changes in levels of B1 and T beta RII mRNA expres sion during peripheral nerve regeneration. Expression of B1 mRNA in th e axotomized hypoglossal motoneurons was substantially decreased from day 3 after axotomy and this decrease was significant until postoperat ive day 28, whereas no T beta RII signal was observed in hypoglossal n ucleus prior or after axotomy. This transient down-regulation of B1 mR NA expression suggests that activin signaling is somehow suppressed du ring peripheral nerve regeneration.