Selective Fasciculation and Divergent Pathfinding Decisions of Embryonic Chick Motor Axons Projecting to Fast and Slow Muscle Regions

Abstract

Proper motor function requires the precise matching of motoneuron and muscle fiber properties. The lack of distinguishing markers for early motoneurons has made it difficult to determine whether this matching is established by selective innervation during development or later via motoneuron-muscle fiber interactions. To examine whether chick motoneurons selectively innervate regions of their target containing either fast or slow muscle fibers, we backlabeled neurons from each of these regions with lipophilic dyes. We found that motor axons projecting to fast and slow muscle regions sorted into separate but adjacent fascicles proximally in the limb, long before they reached the muscle. More distally, these fascicles made divergent pathfinding decisions to course directly to the appropriate muscle fiber region. In contrast, axons projecting to different areas of an all-fast muscle did not fasciculate separately and became more intermingled as they coursed through the limb. Selective fasciculation of fast-and slow-projecting motoneurons was similar both before and after motoneuron cell death, suggesting that motoneurons specifically recognized and fasciculated with axons growing to muscle regions containing the appropriate muscle fiber type. Taken together, these results strongly support the hypothesis that "fast" and "slow" motoneurons are molecularly distinct before target innervation and that they use these differences to selectively fasciculate, pathfind to, and branch within the correct muscle fiber region from the outset of neuromuscular development.

Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development

“…A single neuron is in focus; its axon can be seen leaving the cord, and its dendrites extend some distance medially and laterally (arrowhead). The position of labeled neurons is consistent with the location of the AITIB motor neuron pool (Milner et al, 1998). Inset, In another section, both motor (arrowhead) and sensory (arrow) neurons are labeled by the retrograde tracing.…”

“…Over time, the nerve spreads as a thin sheet covering the lateral surface of the thigh. This pattern corresponds to the position of the anterior iliotibialis, a thin, sheet-like muscle that contains both fast-and slow-twitch muscle fibers (Landmesser, 1978a;Milner et al, 1998). To confirm this identification, we used retrograde DiI labeling in E5.5 embryos to identify the neurons of origin of the dorsal nerve.…”

Gamma and alpha motor neurons distinguished by expression of transcription factor Err3

“…The restriction of Err3 expression to gamma motor neurons provides a molecular reference point for exploring the emergence of neuronal subtype diversity within individual motor pools. We note that anatomical studies suggest that fast and slow motor neurons within a pool exhibit functional distinctions before the point of target muscle innervation (39,40), raising the possibility that this aspect of intrapool diversification also has its origins in differential transcription factor expression.…”

Polysialylated Neural Cell Adhesion Molecule Is Necessary for Selective Targeting of Regenerating Motor Neurons

“…The absence of PMR in NCAM (؊/؊) mice is not attributable to an abnormal distribution of femoral motor axons in mice lacking NCAM Normally, motor axons preferentially cluster in major limb nerves before they exit as a coherent group at the level of their appropriate muscle in birds (Lance-Jones and Landmesser, 1981;Milner et al, 1998), amphibians (Wilson et al, 1988;Brown et al, 1989), and mammals (Browne, 1950;Brown and Booth, 1983). Whether the same degree of motor axon compartmentalization occurs in NCAM (Ϫ/Ϫ) mice is not known.…”