CHARACTERIZATION OF NEUROTROPHIN AND TRK RECEPTOR FUNCTIONS IN DEVELOPING SENSORY GANGLIA - DIRECT NT-3 ACTIVATION OF TRKB NEURONS IN-VIVO

Spinal sensory ganglia have been shown to contain neuronal subpopulati ons with different functions and neurotrophin dependencies. Neurotroph ins act, in targe part, through Trk receptor tyrosine kinases: nerve g rowth factor (NGF) via TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) via TrkB, and neurotrophin-3 (NT-3) via TrkC. In the present paper, we use antibodies to TrkA, TrkB, and TrkC to characterize their expression patterns and to determine which subpo pulations of cells are lost in mice lacking individual neurotrophins o r Trk receptors. Despite previous reports of Trk receptor mRNAs in neu ral crest cells, we detect Trk receptor proteins only in neurons and n ot in neural crest cells or neuronal precursors. Comparisons of neonat al mice deficient in NT-3 or its cognate receptor TrkC have shown that there is a much greater deficiency in spinal sensory neurons in the f ormer, suggesting that NT-3 may activate receptors in addition to TrkC . Using the same antibodies, we show that, during the major period of neurogenesis, NT-3 is required to maintain neurons that express TrkB i n addition to those that express TrkC but is not essential for neurons expressing TrkA. Results also indicate that survival of cells express ing both receptors can be maintained by activation of either one alone . NT-3 can thus activate more than one Trk receptor in vivo, which whe n coexpressed are functionally redundant.