Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity.
Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity.
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DOI：
10.1016/j.neuron.2022.09.021
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发表时间：
2022-12-21
期刊：
影响因子：
16.2
通讯作者：
Bonanomi, Dario
中科院分区：
文献类型：
--
作者：
Martins, Luis F.;Brambilla, Ilaria;Motta, Alessia;de Pretis, Stefano;Bhat, Ganesh Parameshwar;Badaloni, Aurora;Malpighi, Chiara;Amin, Neal D.;Imai, Fumiyasu;Almeida, Ramiro D.;Yoshida, Yutaka;Pfaff, Samuel L.;Bonanomi, Dario
神经系统需要神经血管网络提供代谢物和氧气，但这需要神经元和内皮细胞的紧密结合。我们发现运动神经元通过远程VEGF信号吸引血管，但轴突通路中的内皮细胞是与肌肉建立连接的障碍。目前尚不清楚这种来自异型神经血管接触的矛盾干扰是如何避免的。通过小鼠突变筛选，我们发现神经丛蛋白d1受体在内皮细胞中是神经肌肉连通性发展所必需的。运动神经元释放Sema3C，通过丛状蛋白d1引起短距离排斥，从而取代阻碍轴突生长的内皮细胞。当这一信号通路被破坏时，外轴运动神经元被阻止到达其肌肉目标，同时脊髓中的血管模式被改变。因此，反向推拉信号的综合系统确保避免有害的轴突内皮接触，同时使神经系统内和周围神经的血管化得以实现。轴突在复杂的环境中穿行，与其他细胞的意外相遇可能会阻碍它们的进程。Martins等人发现了一种基于短距离Sema3C/Plexin-D1排斥信号的选择性障碍清除途径，运动神经元利用该途径逃避与血管的碰撞，同时通过内皮细胞的吸引力实现相互依赖的神经血管网络的组装。
The nervous system requires metabolites and oxygen supplied by the neurovascular network, but this necessitates close apposition of neurons and endothelial cells. We find motor neurons attract vessels with long-range VEGF signaling, but endothelial cells in the axonal pathway are an obstacle for establishing connections with muscles. It is unclear how this paradoxical interference from heterotypic neurovascular contacts is averted. Through a mouse mutagenesis screen, we show that Plexin-D1 receptor is required in endothelial cells for development of neuromuscular connectivity. Motor neurons release Sema3C to elicit short-range repulsion via Plexin-D1, thus displacing endothelial cells that obstruct axon growth. When this signaling pathway is disrupted, epaxial motor neurons are blocked from reaching their muscle targets and concomitantly vascular patterning in the spinal cord is altered. Thus, an integrative system of opposing push-pull cues ensures detrimental axon-endothelial encounters are avoided while enabling vascularization within the nervous system and along peripheral nerves. Axons navigate complex environments where unwanted encounters with other cells might hinder their course. Martins et al. identify a selective obstacle-removal pathway based on short-range Sema3C/Plexin-D1 repulsive signaling that motor neurons employ to evade collisions with blood vessels while enabling assembly of interdependent neurovascular networks through attraction of endothelial cells.
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影响因子：
64.5
作者：
Bonanomi D;Chivatakarn O;Bai G;Abdesselem H;Lettieri K;Marquardt T;Pierchala BA;Pfaff SL
通讯作者：
Pfaff SL
DOI：
10.1126/science.aad2509
发表时间：
2015-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amin ND;Bai G;Klug JR;Bonanomi D;Pankratz MT;Gifford WD;Hinckley CA;Sternfeld MJ;Driscoll SP;Dominguez B;Lee KF;Jin X;Pfaff SL
通讯作者：
Pfaff SL
DOI：
10.1073/pnas.0900222106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Dray, Cyril;Rougon, Genevieve;Debarbieux, Franck
通讯作者：
Debarbieux, Franck
影响因子：
16.2
作者：
Feiner, L;Koppel, AM;Raper, JA
通讯作者：
Raper, JA
影响因子：
16.2
作者：
Bonanomi, Dario;Valenza, Fabiola;Pfaff, Samuel L.
通讯作者：
Pfaff, Samuel L.