Zinc-finger gene Fez in the olfactory sensory neurons regulates development of the olfactory bulb non-cell-autonomously.
Fez is a zinc-finger gene encoding a transcriptional repressor that is expressed in the olfactory epithelium, hypothalamus, ventrolateral pallium and prethalamus at mid-gestation. To reveal its function, we generated Fez-deficient mice. The Fez-deficient mice showed several abnormalities in the olfactory system: (1) impaired axonal projection of the olfactory sensory neurons; (2) reduced size of the olfactory bulb; (3) abnormal layer formation in the olfactory bulb; and (4) aberrant rostral migration of the interneuron progenitors. Fez was not expressed in the projection neurons, interneurons or interneuron progenitors. Transgene-mediated expression of Fez in olfactory sensory neurons significantly rescued the abnormalities in olfactory axon projection and in the morphogenesis of the olfactory bulb in Fez-knockout mice. Thus, Fez is cell-autonomously required for the axon termination of olfactory sensory neurons, and Fez non-cell-autonomously controls layer formation and interneuron development in the olfactory bulb. These findings suggest that signals from olfactory sensory neurons contribute to the proper formation of the olfactory bulb.
Laboratory for Vertebrate Axis Formation, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Tsutomu
T
Hirata
Masato
M
Nakazawa
Sei-ichi
S
Yoshihara
Hitoshi
H
Miyachi
Kunio
K
Kitamura
Yoshihiro
Y
Yoshihara
Masahiko
M
Hibi
D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D005260:Female; D007395:Interneurons / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C412364:Zfp312 protein, mouse