Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2-dependent and -independent pathways
- Campbell, D.S., Stringham, S.A., Timm, A., Xiao, T., Law, M.Y., Baier, H., Nonet, M.L., and Chien, C.B.
- Neuron 55(2): 231-245 (Journal)
- Registered Authors
- Baier, Herwig, Campbell, Douglas, Chien, Chi-Bin, Law, Mei-Yee, Nonet, Michael, Xiao, Tong
- MeSH Terms
- Nerve Tissue Proteins/metabolism*
- Receptors, Immunologic/metabolism*
- Retinal Ganglion Cells/cytology
- Retinal Ganglion Cells/metabolism*
- Superior Colliculi/cytology
- Superior Colliculi/metabolism
- Visual Pathways/cytology
- Visual Pathways/metabolism*
- Zebrafish Proteins/metabolism*
- 17640525 Full text @ Neuron
Campbell, D.S., Stringham, S.A., Timm, A., Xiao, T., Law, M.Y., Baier, H., Nonet, M.L., and Chien, C.B. (2007) Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2-dependent and -independent pathways. Neuron. 55(2):231-245.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes