NEUROTROPHIN-3 SUPPORTS THE SURVIVAL OF DEVELOPING MUSCLE SENSORY NEURONS IN CULTURE

Target-dependent cell death of different subpopulations of sensory neurons may be regulated by different trophic factors. To investigate this possibility, we have taken advantage of the fact that the fractions of muscle sensory and cutaneous sensory neurons in chicken dorsal root ganglia (DRG) are probably different at different segmental levels, and we have compared the responses of chicken DRG from levels that do and do not innervate limb tissue to various growth factors in vitro. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) both supported neurite outgrowth from DRG explanted from all segmental levels. In contrast, neurotrophin 3 (NT-3) supported robust neurite growth only from DRG explanted from the cervical or lumbar levels, which innervate limb muscles. Similarly, NGF and BDNF both promoted survival of dissociated neurons from limb and nonlimb segmental levels, whereas NT-3 promoted survival of more neurons from limb compared to nonlimb levels. This suggests that muscle sensory neurons, which are probably more prevalent at the cervical and lumbar levels, may be specifically affected by NT-3. To evaluate this possibility directly, we compared the survival of retrogradely labeled muscle and cutaneous neurons in NGF, BDNF, and NT-3. Identified muscle sensory neurons survived best in vitro in the presence of NT-3, while the survival of identified cutaneous sensory neurons was greatest in NGF. This work provides direct evidence for a potential role of NT-3 versus NGF in the survival of a specific subpopulation of DRG neurons.