The proto-oncogene BCL6 promotes survival of olfactory sensory neurons.
For the mammalian olfactory epithelium to continually detect odorant, neuronal survival, apoptosis, and regeneration must be coordinated. Here, we showed that the proto-oncogene BCL6, which encodes a transcriptional repressor required for lymphocyte terminal differentiation, contributes to the survival of olfactory sensory neurons (OSNs). In the olfactory epithelia of the BCL6 null mutant mice, many OSNs were positive for both OMP and GAP43. The epithelium was relatively thinner, showing many apoptotic signals. These characters were phenotypically similar to those of the wild-type mice treated with nasal lectin irrigation, which acutely induces apoptosis of OSNs. Odorant receptors were expressed normally in the epithelia of the mutant mice, and their overall expression profile based on DNA microarray analyses was roughly similar to that of the apoptosis-induced olfactory epithelia of the wild-type mice. Experimental increase of BCL6 together with green fluorescent protein in OSNs using adenovirus-mediated gene transfer made the epifluorescence last longer than the control fluorescence without exogenous BCL6 after the nasal lectin irrigation, indicating that BCL6 made the infected neurons survive longer. We conclude that BCL6 plays an active role in the survival of OSNs as an anti-apoptotic factor and confers immature OSNs enough time to fully differentiate into mature ones.
The BCPH Unit of Molecular Physiology, Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa, Japan. otaki@sci.u-ryukyu.ac.jp
Joji M
JM
Otaki
Masahiko
M
Hatano
Rie
R
Matayoshi
Takeshi
T
Tokuhisa
Haruhiko
H
Yamamoto
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D037102:Lectins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051842:Olfactory Marker Protein / Q000235:genetics / Q000378:metabolism; D009831:Olfactory Mucosa / Q000473:pathology / Q000502:physiology*; D009929:Organ Size; D051560:Proto-Oncogene Proteins c-bcl-6; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000473:pathology / Q000502:physiology*
C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; D037102:Lectins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D018035:Receptors, Odorant