title: The oriented emergence of axons from retinal ganglion cells is directed by laminin contact in vivo.
abstract: How the site of axon emergence is specified during neural development is not understood. Previous studies disagree on the relative importance of intrinsic and extrinsic mechanisms. The axons of retinal ganglion cells (RGCs) emerge basally in vivo, yet because RGCs develop from polarized neuroepithelial cells within a polarized environment, disentangling intrinsic and extrinsic influences is a challenge. We use time-lapse imaging to demonstrate that Laminin acting directly on RGCs is necessary and sufficient to orient axon emergence in vivo. Laminin contact with the basal processes of newborn RGCs prevents the cells from entering a stochastic Stage 2 phase, directs the rapid accumulation of the early axonal marker Kif5c560-YFP, and leads to the formation of axonal growth cones. These results suggest that contact-mediated cues may be critical for the site of axon emergence and account for the differences in cellular behavior observed in vitro and in vivo.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Owen
authors.initials: O
authors.lastname: Randlett
authors.forename: Lucia
authors.initials: L
authors.lastname: Poggi
authors.forename: Flavio R
authors.initials: FR
authors.lastname: Zolessi
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018385:Centrosome / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D007797:Laminin / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging / Q000379:methods; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D007797:Laminin; D008164:Luminescent Proteins; D009418:S100 Proteins; D029961:Zebrafish Proteins; C413414:atoh7 protein, zebrafish