Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling
Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling
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DOI：
10.1016/j.neuron.2008.12.026
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发表时间：
2009-03-12
期刊：
影响因子：
16.2
通讯作者：
Jessell, Thomas M.
中科院分区：
文献类型：
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作者：
Agalliu, Dritan;Takada, Shinji;Jessell, Thomas M.
轴向肌肉由中位运动柱 (MMC) 的运动神经元支配。与支配肢体、体壁和神经元目标的节段性受限运动柱不同，MMC 神经元是沿着脊髓的整个长度产生的。我们表明，MMC 命运的规范涉及由底板内和周围表达的三种 Wnt 蛋白（Wnt4、Wnt5a 和 Wnt5b）介导的背腹信号传导程序。这些令状似乎建立了腹侧（高）到背侧（低）的信号梯度，并通过维持脊髓运动神经元中 LIM 同源域蛋白 Lhx3/4 的表达来促进 MMC 身份和连接性。 Wnt4/5 活性的升高会产生额外的 MMC 神经元，但会牺牲其他运动神经元柱状亚型，而 Wnt4/5 活性的降低会抑制 MMC 神经元的产生。因此，需要由Shh和Wnt4/5介导的两条背腹信号通路来建立运动神经元柱状身份的早期二元分歧。
Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Writs appear to establish a ventral(high) to dorsal(low) signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.