Emerging evidence for cell-autonomous axon guidance.,Development, Growth & Differentiation

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Emerging evidence for cell-autonomous axon guidance.
Development, Growth & Differentiation ( IF 1.7 ) Pub Date : 2020-04-12 , DOI: 10.1111/dgd.12666
Hidekiyo Harada ₁ , Jason Charish ₁ , Philippe P Monnier _{1,

2}

Affiliation

Current models of axon guidance within the central nervous system (CNS) involve the presentation of environmental cues to navigating growth cones. The surrounding and target tissues present a variety of ligands that either restrict or promote growth, thus providing pathfinding instructions to developing axons. Recent findings show that RGMb, a GPI anchored extracellular protein present on retinal ganglion cells, down‐regulates Wnt3a signaling by lowering LRP5 levels at the membrane surface. When RGMb is phosphorylated by the extracellular tyrosine kinase VLK, phosphorylated RGMb (p‐RGMb) is internalized and carries LRP5 towards intracellular compartments. In the eye, a dorsal‐high ventral‐low gradient of VLK generates a dorsal‐low ventral‐high gradient of LRP5 that modulates Wnt3a signaling. These molecules, which are all expressed by individual RGCs, generate Wnt‐signal gradients along the dorso‐ventral axis of the retina, resulting in differential axon growth which in turn regulates proper retino‐tectal/collicular map formation. This pathway represents a regulatory mechanism whereby extracellular phosphorylation generates what may be the first example of a unique self‐guiding mechanism that affects neuronal‐target connections independent of paracrine signals from the surrounding target tissue.

中文翻译：

细胞自主轴突指导的新证据。

当前在中枢神经系统（CNS）中的轴突引导模型涉及到环境提示到生长锥的导航。周围和目标组织呈现出多种限制或促进生长的配体，从而为发育中的轴突提供了寻路指导。最近的发现表明，视网膜神经节细胞上存在的GPI锚定的细胞外蛋白RGMb通过降低膜表面LRP5水平来下调Wnt3a信号传导。当RGMb被细胞外酪氨酸激酶VLK磷酸化时，磷酸化的RGMb（p-RGMb）被内化并向细胞内区室携带LRP5。在眼中，VLK的背高腹侧低梯度生成LRP5的背腹低腹高梯度，从而调节Wnt3a信号传导。这些分子所有这些都由单个RGC表示，沿着视网膜的背腹轴产生Wnt信号梯度，导致轴突的差异生长，进而调节适当的视网膜-枕骨/胶原图形成。该途径代表一种调节机制，细胞外磷酸化可产生独特的自我指导机制的第一个例子，该机制可独立于周围目标组织的旁分泌信号而影响神经元与目标的连接。

更新日期：2020-04-12

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