Programs in Neuroscience, Department of Physiology, University of California, San Francisco, 1550 Fourth Street, San Francisco, CA 94158-2722, USA.
Cell. 2011 Jul 8;146(1):164-76. doi: 10.1016/j.cell.2011.06.016.
The mechanisms that generate specific neuronal connections in the brain are under intense investigation. In zebrafish, retinal ganglion cells project their axons into at least six layers within the neuropil of the midbrain tectum. Each axon elaborates a single, planar arbor in one of the target layers and forms synapses onto the dendrites of tectal neurons. We show that the laminar specificity of retinotectal connections does not depend on self-sorting interactions among RGC axons. Rather, tectum-derived Slit1, signaling through axonal Robo2, guides neurites to their target layer. Genetic and biochemical studies indicate that Slit binds to Dragnet (Col4a5), a type IV Collagen, which forms the basement membrane on the surface of the tectum. We further show that radial glial endfeet are required for the basement-membrane anchoring of Slit. We propose that Slit1 signaling, perhaps in the form of a superficial-to-deep gradient, presents laminar positional cues to ingrowing retinal axons.
大脑中产生特定神经元连接的机制正在深入研究。在斑马鱼中，视网膜神经节细胞将其轴突投射到中脑顶盖神经叶的神经间质中至少六个层中。每个轴突在一个靶层中精心制作单个平面树突，并在顶盖神经元的树突上形成突触。我们表明，视网膜顶盖连接的层特异性不依赖于 RGC 轴突之间的自我排序相互作用。相反，顶盖衍生的 Slit1 通过轴突 Robo2 发出信号，引导神经突到达其靶层。遗传和生化研究表明，Slit 与 Dragnet（Col4a5）结合，后者是 IV 型胶原蛋白，在顶盖表面形成基膜。我们进一步表明，放射状神经胶质足突对于 Slit 的基膜锚定是必需的。我们提出 Slit1 信号，可能以浅层到深层的梯度形式，向生长中的视网膜轴突呈现层状位置线索。
