Slit1a Inhibits Retinal Ganglion Cell Arborization and Synaptogenesis via Robo2-Dependent and -Independent Pathways

Douglas Simon Campbell, Sydney A. Stringham, Adam Timm, Tong Xiao, Mei Yee Law, Herwig Baier, Michael L. Nonet, Chi Bin Chien

研究成果: Article

64 引用 (Scopus)

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Upon arriving at their targets, developing axons cease pathfinding and begin instead to arborize and form synapses. To test whether CNS arborization and synaptogenesis are controlled by Slit-Robo signaling, we followed single retinal ganglion cell (RGC) arbors over time. ast (robo2) mutant and slit1a morphant arbors had more branch tips and greater arbor area and complexity compared to wild-type and concomitantly more presumptive presynaptic sites labeled with YFP-Rab3. Increased arborization in ast was phenocopied by dominant-negative Robo2 expressed in single RGCs and rescued by full-length Robo2, indicating that Robo2 acts cell-autonomously. Time-lapse imaging revealed that ast and slit1a morphant arbors stabilized earlier than wild-type, suggesting a role for Slit-Robo signaling in preventing arbor maturation. Genetic analysis showed that Slit1a acts both through Robo2 and Robo2-independent mechanisms. Unlike previous PNS studies showing that Slits promote branching, our results show that Slits inhibit arborization and synaptogenesis in the CNS.

元の言語English
ページ(範囲)231-245
ページ数15
ジャーナルNeuron
55
発行部数2
DOI
出版物ステータスPublished - 2007 7 19
外部発表Yes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Campbell, D. S., Stringham, S. A., Timm, A., Xiao, T., Law, M. Y., Baier, H., Nonet, M. L., & Chien, C. B. (2007). Slit1a Inhibits Retinal Ganglion Cell Arborization and Synaptogenesis via Robo2-Dependent and -Independent Pathways. Neuron, 55(2), 231-245. https://doi.org/10.1016/j.neuron.2007.06.034