Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Neuroscience. 2020 Dec 1;450:29-47. doi: 10.1016/j.neuroscience.2020.09.054. Epub 2020 Oct 8.
Precise control of limb muscles, and ultimately of limb movement, requires accurate motor innervation. Motor innervation of the vertebrate limb is established by sequential selection of trajectories at successive decision points. Motor axons of the lateral motor column (LMC) segregate at the base of the limb into two groups that execute a choice between dorsal and ventral tissue: medial LMC axons innervate the ventral limb, whereas lateral LMC axons innervate the dorsal limb. We investigated how LMC axons are targeted to the limb using the chick mutant limbless (ll), which has a dorsal transformation of the ventral limb mesenchyme. In ll the spatial pattern of motor projections to the limb is abnormal while their targeting is normal. While extensive, the dorsal transformation of the ll ventral limb mesenchyme is incomplete whereas the generation, specification and targeting of spinal motor neurons are apparently unaffected. Thus, the dorsal-ventral motor axon segregation is an active choice that is independent of the ratio between dorsal and ventral tissue but dependent on the presence of both tissues. Therefore, the fidelity of the motor projections to the limb depends on the presence of both dorsal and ventral compartments, while the geometry of motor projections is controlled by the position of limb dorsal-ventral compartment boundary.
精确控制肢体肌肉，最终实现肢体运动，需要精确的运动神经支配。脊椎动物肢体的运动神经支配是通过在连续的决策点上依次选择轨迹来建立的。外侧运动柱（LMC）的运动轴突在肢体的基部分离成两组，在背侧和腹侧组织之间进行选择：内侧 LMC 轴突支配肢体的腹侧，而外侧 LMC 轴突支配肢体的背侧。我们使用 chick 突变体 limbless（ll）研究了 LMC 轴突如何靶向肢体，该突变体的腹侧肢体间充质发生了背侧转化。在 ll 中，肢体的运动投射的空间模式异常，而其靶向是正常的。虽然 ll 腹侧肢体间充质的背侧转化很广泛，但脊髓运动神经元的产生、特化和靶向显然没有受到影响。因此，背侧-腹侧运动轴突的分离是一种主动选择，它独立于背侧和腹侧组织的比例，但依赖于两者的存在。因此，运动投射到肢体的保真度取决于背侧和腹侧隔室的存在，而运动投射的几何形状则由肢体背-腹隔室边界的位置控制。
