DEVELOPMENT OF BONE MORPHOGENETIC PROTEIN RECEPTORS IN THE NERVOUS-SYSTEM AND POSSIBLE ROLES IN REGULATING TRKC EXPRESSION

Characterization of bone morphogenetic protein receptor (BMPR) express ion during development is necessary for understanding the role of thes e factors during neural maturation. In this study, in situ hybridizati on analyses demonstrate that BMP-specific type I (BMPR-IA and BMPR-IB) and type II (BMPR-II) receptor mRNAs are expressed at significant lev els in multiple regions of the CNS, cranial ganglia, and peripheral se nsory and autonomic ganglia during the embryonic and neonatal periods. All three BMP receptor subunits are expressed within periventricular generative zones. BMPR-IA is more abundant than the other receptor sub types, with widespread expression in the brain, crania[ ganglia, and p eripheral ganglia. By contrast, BMPR-IB mRNA displays significant expr ession within more restricted regions, including the anterior olfactor y nuclei. BMPR-II mRNA exhibits peak expression within the cerebellar Purkinje cell layer and the hippocampus, as well as within cranial gan glia. The distribution of BMP receptors within large neurons in adult dorsal root ganglia suggested a possible role in regulating expression of the neurotrophin receptor trkC. This hypothesis was tested in expl ant cultures of embryonic day 15 (E15) and postnatal day 1 (P1) sympat hetic superior cervical ganglia (SCG). Treatment of the E15 or the P1 SCG with BMP-2 induced expression of trkC mRNA and responsiveness of s ympathetic neurons to NT3 as measured by neurite outgrowth. The patter n of expression of BMP receptors in embryonic brain suggests several p otentially novel areas for further developmental analysis and supports numerous recent studies that indicate that BMPs have a broad range of cellular functions during neural development and in adult life.