Effects of neurotrophin-3 gene mutation in the expression of neurocalcin

Abstract

Neurocalcin (NC) is a neuron-specific "EF-hand" calcium-binding protein present in a non-fully characterized subpopulation of dorsal root ganglion (DRG) neurons, some kinds of mechanoreceptors and proprioceptors, and in motor end-plates. In the present study we have characterized NC expression in spinal sensory and motor neurons, and their endings in newborn mouse. Because the neurotrophic factor neurotrophin-3 (NT-3) appears to plays a major role in the development and maturation of sensory and motor neuronal populations, we have studied NC immunoreactivity in newborn NT-3 null mutant. In NT-3 deficient animals the overall number of NC-immunoreactive DRG neurons was reduced by as much as 70% including all large neurons, but subpopulations of NC expressing small and intermediate-sized neurons survived. As expected no muscle spindles were found in NT-3 mutant mice while they were present and normally innervated by NC-positive nerve fibers in wild-type animals. On the other hand, NC immunoreactivity was dramatically decreased in motoneurons of the spinal cord, ventral root nerves and motor end-plates in the absence of NT-3. The present results demonstrate that NC-containing DRG neurons include all proprioceptive, and a subset of mechanoreceptive and proprioceptive. Furthermore, they strongly suggest that NT-3 is involved in the maturation of motor end-plates.