REDUCTION IN THE NUMBER OF SPINAL MOTOR-NEURONS IN NEUROTROPHIN-3-DEFICIENT MICE

The effects of a deficiency of neurotrophin-3 on spinal motor neurons were assessed by determining the number of myelinated nerve fibers in lumbar ventral spinal roots of mice with a deletion in the neurotrophin-3 gene. Few or no small-caliber (fusimotor) nerve fibers were present in the L4 ventral root of homozygous mutant mice lacking both copies of the neurotrophin-3 gene, and approximately one-half of the normal complement of the fibers was present in heterozygous mice having one copy of the neurotrophin-3 gene relative to wild type mice at two weeks of age. Numbers of fusimotor nerve fibers paralleled numbers of muscle spindles, the target organs of fusimotor innervation, in hindlimb muscles. Muscle spindles and intrafusal fibers were absent in the soleus muscles of homozygous mutants, and were reduced by approximately 50% in heterozygous relative to wild type mice in accord with previous reports. Neurotrophin-3 might be generated by the intrafusal fibers and may provide a target-derived neurotrophic support for developing fusimotor neurons because in the absence of muscle spindles the neurons did not differentiate and/or survive. In contrast, a great majority of skeletomotor neurons that innervate extrafusal muscle fibers differentiated normally in the absence of neurotrophin-3. This study, analysed in conjunction with our previously reported data, suggests that neurotrophin-3 acts in a coordinated fashion to support, either directly or indirectly, the development of each of the three classes of cells-Ia and Ib sensory neurons, fusimotor neurons, and intrafusal muscle fibers-that comprise the limb proprioceptive system.