title: Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2-dependent and -independent pathways.
abstract: 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.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, UT 84132, USA. douglas.campbell@cantab.net
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Campbell
authors.forename: Sydney A
authors.initials: SA
authors.lastname: Stringham
authors.forename: Adam
authors.initials: A
authors.lastname: Timm
authors.forename: Tong
authors.initials: T
authors.lastname: Xiao
authors.forename: Mei-Yee
authors.initials: MY
authors.lastname: Law
authors.forename: Herwig
authors.initials: H
authors.lastname: Baier
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nonet
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins; C492287:slit1a protein, zebrafish