Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1.
Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1.
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DOI：
10.1186/1749-8104-4-21
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发表时间：
2009-06-19
影响因子：
3.6
通讯作者：
Klar A
中科院分区：
文献类型：
--
作者：
Avraham O;Hadas Y;Vald L;Zisman S;Schejter A;Visel A;Klar A
Lim-HD蛋白控制神经元分化的关键方面，包括亚型身份和轴突导向。Lim-HD蛋白Lhx 2/9和Lhx 1/5分别在背侧脊髓中间神经元群体dI 1和dI 2中表达。虽然它们不是细胞命运获取所必需的，但它们在dI 1和dI 2神经元轴突轨迹模式化中的作用仍不完全清楚。使用新发现的dI 1和dI 2特异性增强子追踪源自这些中间神经元的轴突轨迹，我们发现每个群体根据其轴突通路被细分为几个不同的组。dI 1神经元在同侧或对侧向吻侧投射轴突，而dI 2主要是连合神经元，其向吻侧和尾侧投射其轴突。每个神经元群体的纵向轴突轨迹自成束形成dI 1和dI 2特异性束。dI 1束相对于dI 2束在空间上位于腹侧。为了研究Lim-HD蛋白对建立dI轴突投射的功能贡献，通过细胞特异性异位表达改变了dI神经元的Lim-HD编码。Lhx 1在dI 1神经元中的表达引起Lhx 2/9的抑制，并向尾侧连合dI 1神经元施加尾侧投射。互补地，当在dI 2神经元中表达时，Lhx 9抑制Lhx 1/5，并触发偏向于在其他尾侧投射的dI 2神经元中的吻侧投射，以及纵向轴索束的腹侧移位。Lim-HD蛋白Lhx 9和Lhx 1作为一个二元开关，控制尾连合轴突的头侧与尾侧纵向转向。Lhx 1决定尾侧转向，Lhx 9触发喙侧转向。
Lim-HD proteins control crucial aspects of neuronal differentiation, including subtype identity and axonal guidance. The Lim-HD proteins Lhx2/9 and Lhx1/5 are expressed in the dorsal spinal interneuron populations dI1 and dI2, respectively. While they are not required for cell fate acquisition, their role in patterning the axonal trajectory of dI1 and dI2 neurons remains incompletely understood. Using newly identified dI1- and dI2-specific enhancers to trace axonal trajectories originating from these interneurons, we found that each population is subdivided into several distinct groups according to their axonal pathways. dI1 neurons project axons rostrally, either ipsi- or contra-laterally, while dI2 are mostly commissural neurons that project their axons rostrally and caudally. The longitudinal axonal tracks of each neuronal population self-fasciculate to form dI1- and dI2-specific bundles. The dI1 bundles are spatially located ventral relative to dI2 bundles. To examine the functional contribution of Lim-HD proteins to establishment of dI axonal projections, the Lim-HD code of dI neurons was altered by cell-specific ectopic expression. Expression of Lhx1 in dI1 neurons caused a repression of Lhx2/9 and imposed caudal projection to the caudal commissural dI1 neurons. Complementarily, when expressed in dI2 neurons, Lhx9 repressed Lhx1/5 and triggered a bias toward rostral projection in otherwise caudally projecting dI2 neurons, and ventral shift of the longitudinal axonal fascicule. The Lim-HD proteins Lhx9 and Lhx1 serve as a binary switch in controlling the rostral versus caudal longitudinal turning of the caudal commissural axons. Lhx1 determines caudal turning and Lhx9 triggers rostral turning.