A conserved organizational and functional principle of neural networks is the segregation of axon-dendritic synaptic connections into laminae. Here we report that targeting of synaptic laminae by retinal ganglion cell (RGC) arbors in the vertebrate visual system is regulated by a signaling system relying on target-derived Reelin and VLDLR/Dab1a on the projecting neurons. Furthermore, we find that Reelin is distributed as a gradient on the target tissue and stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM). Through genetic manipulations, we show that this Reelin gradient is important for laminar targeting and that it is attractive for RGC axons. Finally, we suggest a comprehensive model of synaptic lamina formation in which attractive Reelin counter-balances repulsive Slit1, thereby guiding RGC axons toward single synaptic laminae. We establish a mechanism that may represent a general principle for neural network assembly in vertebrate species and across different brain areas.

中文翻译：

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有吸引力的Reelin渐变在脊椎动物的视觉系统中建立了突触分层。

神经网络的保守的组织和功能原理是将轴突-树突突触连接分离成薄片。在这里我们报告说，在脊椎动物视觉系统中，视网膜神经节细胞（RGC）轴对突触层的靶向作用受依赖于投射神经元的靶标Reelin和VLDLR / Dab1a的信号传导系统的调节。此外，我们发现Reelin以梯度分布在目标组织上，并由细胞外基质（ECM）中的硫酸乙酰肝素蛋白聚糖（HSPG）稳定。通过遗传操作，我们表明该Reelin梯度对于层流靶向很重要，并且对于RGC轴突很有吸引力。最后，我们提出了一个完整的突触层形成模型，其中有吸引力的Reelin平衡了排斥性Slit1，从而将RGC轴突引导至单个突触层。我们建立了一种机制，可以代表脊椎动物物种和不同大脑区域的神经网络装配的一般原理。