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

Shizue Ohsawa1, Shun Hamada, Keisuke Kuida

  • 1Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|July 14, 2010
PubMed

Insights

Apoptotic caspases also regulate non-apoptotic functions. Apaf-1/caspase-9 signaling guides olfactory sensory neuron development, including axonal projection and synapse formation, via Semaphorin 7A cleavage.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Caspases are known for their role in apoptosis.
  • Emerging evidence suggests non-apoptotic functions for caspases, particularly in Drosophila.
  • The role of caspases in mammalian nervous system development is largely unknown.

Purpose of the Study:

  • To investigate the non-apoptotic role of Apaf-1/caspase-9 signaling in mammalian nervous system development.
  • To elucidate the specific developmental processes regulated by this pathway in olfactory sensory neurons.

Main Methods:

  • Utilized mutant mice deficient for Apaf-1 or caspase-9.
  • Examined axonal projection, synapse formation, and neuronal maturation in olfactory sensory neurons.
  • Investigated the cleavage of Semaphorin 7A as a downstream target.

Main Results:

  • Apaf-1/caspase-9 signaling regulates axonal projection, synapse formation, and maturation of olfactory sensory neurons.
  • This pathway mediates the cleavage of Semaphorin 7A, essential for axonal guidance.
  • Mice lacking Apaf-1 or caspase-9 showed misrouted axons, impaired synapse formation, and defective neuronal maturation without affecting cell numbers.

Conclusions:

  • Apaf-1/caspase-9-mediated non-apoptotic caspase signaling is crucial for proper neural network formation during olfactory development.
  • This pathway plays a vital role in the development and function of olfactory sensory neurons beyond cell death.

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