Milner L D, Rafuse V F, Landmesser L T
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106-4975, USA.
J Neurosci. 1998 May 1;18(9):3297-313. doi: 10.1523/JNEUROSCI.18-09-03297.1998.
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.
正常的运动功能需要运动神经元和肌纤维特性精确匹配。早期运动神经元缺乏特异性标记物，这使得难以确定这种匹配是在发育过程中通过选择性支配建立的，还是后来通过运动神经元与肌纤维的相互作用建立的。为了研究鸡的运动神经元是否选择性地支配其靶标中含有快肌纤维或慢肌纤维的区域，我们用亲脂性染料对这些区域的神经元进行了逆向标记。我们发现，投射到快肌和慢肌区域的运动轴突在肢体近端就分选到不同但相邻的束中，远在它们到达肌肉之前。在更远端，这些束做出不同的路径导向决定，直接通向相应的肌纤维区域。相比之下，投射到全快肌不同区域的轴突不会单独成束，在穿过肢体时相互交织得更多。快投射和慢投射运动神经元的选择性成束在运动神经元细胞死亡前后相似，这表明运动神经元能特异性识别并与生长到含有相应肌纤维类型的肌肉区域的轴突成束。综上所述，这些结果有力地支持了以下假说：“快”和“慢”运动神经元在支配靶标之前在分子水平上就存在差异，并且它们从神经肌肉发育开始就利用这些差异进行选择性成束、导向正确的肌纤维区域并在其中分支。
