Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity.
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.
Ohsawa
Shizue
S
Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Hamada
Shun
S
Kuida
Keisuke
K
Yoshida
Hiroki
H
Igaki
Tatsushi
T
Miura
Masayuki
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005920:Glomerular Mesangium / Q000002:abnormalities / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009833:Olfactory Pathways / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D039961:Semaphorins / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013997:Time Factors
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D039961:Semaphorins; D053148:Caspase 3; D053453:Caspase 9