Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling.
Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling.
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DOI：
10.1371/journal.pbio.1000446
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发表时间：
2010-08-10
期刊：
影响因子：
9.8
通讯作者：
Kania A
中科院分区：
文献类型：
--
作者：
Palmesino E;Rousso DL;Kao TJ;Klar A;Laufer E;Uemura O;Okamoto H;Novitch BG;Kania A
在脊椎动物运动系统的胚胎发育过程中，调节轴突轨迹的相同转录因子也可以调节细胞体迁移，从而控制地形图的形成。地形神经元地图出现的结果轴突轨迹的选择与神经元索马的本地化，但身份的途径协调这些过程是未知的。我们解决了这个问题的背景下，近视地图的四肢肌肉支配脊髓外侧运动柱（LMC）运动轴突的Eph受体信号指定生长锥轨迹的Foxp1和Lhx1转录因子的限制。我们发现，本地化的LMC神经元细胞体可以解离轴突轨迹的选择，无论是损失或获得的功能的Reelin信号通路。LMC运动神经元对Reelin的反应是通过Foxp1和Lhx1介导的关键Reelin信号传导中间体Dab1的表达调控来门控的。总之，这些观察结果指向相同的转录因子，控制运动轴突的指导和索马迁移，并揭示了近视组织的分子层次。我们神经系统的许多区域都是以拓扑方式组织的，因此神经元相对于其邻居的位置通常与其轴突轨迹以及目标身份在空间上相关。在这项研究中，我们专注于脊髓近视地图，其特征在于与其轴突到肢体肌肉的轨迹相关的运动神经元细胞体的刻板组织。一个悬而未决的问题是如何形成这个地图是协调神经元迁移和轴突导向效应器的表达的分子的身份。在这里，我们首先表明，Dab1，一个关键的蛋白质，中继信号指导神经元迁移，表达在不同浓度的特定群体的肢体支配运动神经元，并确定其细胞体在脊髓中的位置。然后，我们证明，Foxp1和Lhx1，相同的转录因子，调节运动轴突导向信号的受体的表达，也调节Dab1的表达。我们的研究结果的意义是，我们确定了一个分子层次连接神经元迁移和轴突投射的效应，因此协调神经元索马的位置与轴突轨迹的选择。总的来说，我们的研究结果提供了一个框架，在其中解决神经系统是如何组织的一般问题。
During embryonic development of the vertebrate motor system, the same transcription factors that regulate axonal trajectories can also regulate cell body migration, thereby controlling topographic map formation. Topographic neuronal maps arise as a consequence of axon trajectory choice correlated with the localisation of neuronal soma, but the identity of the pathways coordinating these processes is unknown. We addressed this question in the context of the myotopic map formed by limb muscles innervated by spinal lateral motor column (LMC) motor axons where the Eph receptor signals specifying growth cone trajectory are restricted by Foxp1 and Lhx1 transcription factors. We show that the localisation of LMC neuron cell bodies can be dissociated from axon trajectory choice by either the loss or gain of function of the Reelin signalling pathway. The response of LMC motor neurons to Reelin is gated by Foxp1- and Lhx1-mediated regulation of expression of the critical Reelin signalling intermediate Dab1. Together, these observations point to identical transcription factors that control motor axon guidance and soma migration and reveal the molecular hierarchy of myotopic organisation. Many areas of our nervous system are organized in a topographic manner, such that the location of a neuron relative to its neighbors is often spatially correlated with its axonal trajectory and therefore target identity. In this study, we focus on the spinal myotopic map, which is characterized by the stereotyped organization of motor neuron cell bodies that is correlated with the trajectory of their axons to limb muscles. An open question for how this map forms is the identity of the molecules that coordinate the expression of effectors of neuronal migration and axonal guidance. Here, we first show that Dab1, a key protein that relays signals directing neuronal migration, is expressed at different concentrations in specific populations of limb-innervating motor neurons and determines the position of their cell bodies in the spinal cord. We then demonstrate that Foxp1 and Lhx1, the same transcription factors that regulate the expression of receptors for motor axon guidance signals, also modulate Dab1 expression. The significance of our findings is that we identify a molecular hierarchy linking effectors of both neuronal migration and axonal projections, and therefore coordinating neuronal soma position with choice of axon trajectory. In general, our findings provide a framework in which to address the general question of how the nervous system is organized.
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影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
5.3
作者：
Higashi, S;Hioki, K;Molnár, Z
通讯作者：
Molnár, Z
影响因子：
5.3
作者：
FERNS, MJ;HOLLYDAY, M
通讯作者：
HOLLYDAY, M
DOI：
10.1016/0169-328x(96)00046-0
发表时间：
1996-07-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
DArcangelo, G;Miao, GG;Curran, T
通讯作者：
Curran, T
影响因子：
5.3
作者：
Kao, Tzu-Jen;Palmesino, Elena;Kania, Artur
通讯作者：
Kania, Artur