title: Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization.
abstract: In addition to being critical for apoptosis, components of the apoptotic pathway, such as caspases, are involved in other physiological processes in many types of cells, including neurons. However, very little is known about their role in dynamic, nonphysically destructive processes, such as axonal arborization and synaptogenesis. We show that caspases were locally active in vivo at the branch points of young, dynamic retinal ganglion cell axonal arbors but not in the cell body or in stable mature arbors. Caspase activation, dependent on Caspase-3, Caspase-9, and p38 mitogen-activated protein kinase (MAPK), rapidly increased at branch points corresponding with branch tip addition. Time-lapse imaging revealed that knockdown of Caspase-3 and Caspase-9 led to more stable arbors and presynaptic sites. Genetic analysis showed that Caspase-3, Caspase-9, and p38 MAPK interacted with Slit1a-Robo2 signaling, suggesting that localized activation of caspases lie downstream of a ligand receptor system, acting as key promoters of axonal branch tip and synaptic dynamics to restrict arbor growth in vivo in the central nervous system.
authors.affiliation: Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Campbell
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D060172:Morpholinos / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D060172:Morpholinos; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins; C492287:slit1a protein, zebrafish