NEUROTROPHIN-8 PROMOTES THE DIFFERENTIATION OF MUSCLE-SPINDLE AFFERENTS IN THE ABSENCE OF PERIPHERAL TARGETS

The neurons of the dorsal root ganglia (DRG) that supply muscle spindl es require target-derived factors for survival. One necessary factor f or these neurons is neurotrophin-3 (NT3). To determine whether NT3 can promote the survival of these neurons in the absence of other target- derived factors, we analyzed the effects of exogenous NT3 after early limb bud deletion in the chick. In control embryos, limb bud deletion eliminated similar to 90% of the trkC-positive (trkC+) neurons in lumb ar DRG on the deleted side. In addition, the deletion led to a dramati c loss of collateral sensory projections to motoneurons. Exogenous NT3 restored a normal population of trkC+ neurons in lumbar DRG on the de leted side and increased the number of trkC+ neurons in DRG with norma l targets (contralateral lumbar and thoracic). The effect was highly s elective; NT3 increased the number of trkC+ neurons without significan tly changing the number of either trkA+ or trkB+ neurons. The effect o f NT3 was attributable to the rescue of DRG neurons from cell death, b ecause exogenous NT3 reduced the number of pyknotic nuclei without sig nificantly altering proliferation. Analysis of spinal projections show ed further that many of the trkC+ neurons rescued by NT3 projected to the ventral spinal cord. These neurons thus had central projections ch aracteristic of muscle spindle afferents, Together, our results indica te that NT3 signaling is both necessary and sufficient for the develop ment of the proprioceptive phenotype, even in the absence of other sig nals from limb muscle.