Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity

Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13366-71. doi: 10.1073/pnas.0910488107. Epub 2010 Jul 12.

Abstract

Although the apoptotic role of caspases has been largely understood, accumulating evidence in Drosophila suggests that caspases also control other processes than apoptotic cell death. However, how caspases contribute to the development of the mammalian nervous system remains obscure. Here, we provide unique evidence that Apaf-1/caspase-9-mediated caspase signaling regulates the development of olfactory sensory neurons (OSNs), which includes axonal projection, synapse formation, and maturation of these neurons. This caspase signaling leads to a cleavage of Semaphorin 7A, a membrane-anchored semaphorin that is required for the proper axonal projection. Mutant mice deficient for apaf-1 or caspase-9 exhibit misrouted axons, impaired synaptic formation, and defects in the maturation of OSNs without affecting the number of these cells. Our findings suggest that Apaf-1/caspase-9-mediated nonapoptotic caspase signaling is required for the proper neural network formation during olfactory development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptotic Protease-Activating Factor 1 / genetics
  • Apoptotic Protease-Activating Factor 1 / metabolism*
  • Axons / physiology
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism*
  • Cell Line, Tumor
  • Glomerular Mesangium / abnormalities
  • Glomerular Mesangium / metabolism
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Olfactory Pathways / cytology
  • Olfactory Pathways / embryology
  • Olfactory Pathways / growth & development
  • Semaphorins / metabolism
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction / physiology*
  • Synapses / physiology
  • Time Factors

Substances

  • Apaf1 protein, mouse
  • Apoptotic Protease-Activating Factor 1
  • Semaphorins
  • Caspase 3
  • Caspase 9