BMP9 (bone morphogenetic protein 9) induces NGF as an autocrine/paracrine cholinergic trophic factor in developing basal forebrain neurons.
NGF found in the basal forebrain is believed to be localized to NGF-dependent cholinergic neurons and derived via retrograde axonal transport from NGF-synthesizing target hippocampal and cortical neurons. The basis for this concept of target-derived NGF is the detection of only limited amounts of NGF mRNA in the basal forebrain, despite relatively high NGF levels there. Our work, using a more sensitive and quantitative RNase protection method for detecting relative NGF mRNA levels, suggested, instead, relatively high levels of NGF mRNA synthesis in the septal region of the basal forebrain (BF-S), a region which contained primarily cells that project to the hippocampus. Similar results were obtained in analyses of a larger portion of the basal forebrain, designated "BF," that encompassed cholinergic neurons that project to both the hippocampus and the cortex. The level of NGF mRNA measured in both BF-S and BF was equivalent to approximately 50% of the amount observed in the hippocampus. Furthermore, relative NGF mRNA levels detected in the BF-S, cortex, and hippocampus were shown to be proportional to NGF protein levels quantitated in each region. The detection of relatively high amounts of NGF synthesis in the BF-S was supported in studies demonstrating rapid NGF receptor (Trk) activation in the basal forebrain by exogenous NGF and in experiments showing that NGF mRNA was inducible in the BF-S by 1,25 dihydroxyvitamin D3. The extent of NGF mRNA induction was similar (approximately twofold) in the BF-S, hippocampus, and cortex, suggesting similar regulatory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)