Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization

Douglas Simon Campbell, Hitoshi Okamoto

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)657-672
Number of pages16
JournalJournal of Cell Biology
Volume203
Issue number4
DOIs
Publication statusPublished - 2013 Nov 25
Externally publishedYes

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Caspases
Caspase 9
Caspase 3
p38 Mitogen-Activated Protein Kinases
Time-Lapse Imaging
Physiological Phenomena
Retinal Ganglion Cells
Central Nervous System
Apoptosis
Ligands
Neurons
Growth

ASJC Scopus subject areas

  • Cell Biology

Cite this

Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization. / Campbell, Douglas Simon; Okamoto, Hitoshi.

In: Journal of Cell Biology, Vol. 203, No. 4, 25.11.2013, p. 657-672.

Research output: Contribution to journalArticle

Campbell, Douglas Simon ; Okamoto, Hitoshi. / Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization. In: Journal of Cell Biology. 2013 ; Vol. 203, No. 4. pp. 657-672.
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