A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors
A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors
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DOI：
10.1016/j.neuron.2008.07.020
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发表时间：
2008-08-14
期刊：
影响因子：
16.2
通讯作者：
Dodd, Jane
中科院分区：
文献类型：
--
作者：
Wilson, Sara I.;Shafer, Beth;Dodd, Jane
尽管有越来越多的证据表明神经连接的转录控制，转录因子如何调节轴突引导中的离散步骤仍然不清楚。脊髓背侧的投射神经元将感觉信号传递到更高级的大脑中心。一些投射神经元向同侧发送轴突，而另一些连合神经元向对侧发送轴突。我们发现，两个密切相关的LIM同源结构域蛋白，Lhx 2和Lhx 9，由一组连合中继神经元（DL 1C神经元）和DL 1C轴突投射所需的表达。在Lhx 2/9双突变体中，dl 1c轴突的中线交叉丢失，这是由dl 1c轴突的Rig-1表达丢失引起的缺陷。Lhx 2与Rig-1基因中的保守基序结合，表明Lhx 2/9直接调节Rig-1的表达。我们的研究结果揭示了定义神经元亚型身份的转录程序与指导其轨迹的独特方面的受体表达之间的联系。
Despite increasing evidence for transcriptional control of neural connectivity, how transcription factors regulate discrete steps in axon guidance remains obscure. Projection neurons in the dorsal spinal cord relay sensory signals to higher brain centers. Some projection neurons send their axons ipsilaterally, whereas others, commissural neurons, send axons contralaterally. We show that two closely related LIM homeodomain proteins, Lhx2 and Lhx9, are expressed by a set of commissural relay neurons (dl1c neurons) and are required for the dl1c axon projection. Midline crossing by dl1c axons is lost in Lhx2/9 double mutants, a defect that results from loss of expression of Rig-1 from dl1c axons. Lhx2 binds to a conserved motif in the Rig-1 gene, suggesting that Lhx2/9 regulate directly the expression of Rig-1. Our findings reveal a link between the transcriptional programs that define neuronal subtype identity and the expression of receptors that guide distinctive aspects of their trajectory.