Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 30, Pages 13366-13371Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910488107
Keywords
neural development; nonapoptotic function; axonal projection; synapse formation; Sema7A
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Funding
- Japanese Ministry of Education, Science, Sports, Culture and Technology
- RIKEN Bioarchitect Research Grant
- Japan Society for the promotion of Science for Young Scientists
- Grants-in-Aid for Scientific Research [19109003] Funding Source: KAKEN
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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.
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