An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System
An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System
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DOI：
10.1016/j.neuron.2018.01.030
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发表时间：
2018-03-07
期刊：
影响因子：
16.2
通讯作者：
Del Bene, Filippo
中科院分区：
文献类型：
--
作者：
Di Donato, Vincenzo;De Santis, Flavia;Del Bene, Filippo
神经网络的一个保守的组织和功能原则是将轴突-树突突触连接分离成板层。在这里，我们报道了脊椎动物视觉系统中视网膜神经节细胞(RGC)树枝对突触板层的靶向是由一个依赖于靶向Reelin和投射神经元上的VLDLR/Dab1a的信号系统调节的。此外，我们发现Reelin在靶组织上呈梯度分布，并被细胞外基质(ECM)中的硫酸乙酰肝素蛋白多糖(HSPGs)稳定。通过遗传操作，我们证明了这种Reelin梯度对于板层靶向是重要的，并且对RGC轴突具有吸引力。最后，我们提出了一个全面的突触板层形成模型，在该模型中，吸引力的Reelin抵消了排斥性的Slit1，从而引导RGC轴突走向单一的突触板层。我们建立了一种机制，该机制可能代表了脊椎动物物种和不同脑区神经网络组装的一般原则。
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.