title: Assembly of lamina-specific neuronal connections by slit bound to type IV collagen.
abstract: 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.
authors: Programs in Neuroscience, Department of Physiology, University of California, San Francisco, 1550 Fourth Street, San Francisco, CA 94158-2722, USA.
authors: Tong
authors: T
authors: Xiao
authors: Wendy
authors: W
authors: Staub
authors: Estuardo
authors: E
authors: Robles
authors: Nathan J
authors: NJ
authors: Gosse
authors: Gregory J
authors: GJ
authors: Cole
authors: Herwig
authors: H
authors: Baier
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015398:Signal Transduction; D003336:Tectum Mesencephali / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D024141:Collagen Type IV; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins