Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice.
Heat shock transcription factors (HSFs) play roles not only in heat shock response but also in development of the reproductive organs, brain, and lens. Here, we analyzed sensory organs and found abnormalities of the olfactory epithelium in adult HSF1-null mice, which is developmentally related to the lens. The olfactory epithelium was normal until postnatal 3 weeks but was not maintained later than 4 weeks in HSF1-null mice. The olfactory epithelium was atrophied with increased cell death of olfactory sensory neurons. Analysis of the epithelium revealed that induction of HSP expression and reduction of LIF expression are lacking in adult HSF1-null mice. We found that DNA binding activity of HSF1 is induced in the olfactory epithelium later than 4 weeks and that HSF1 binds directly to Lif gene and inhibits its expression. HSF4 has opposing effects on LIF expression and olfactory neurogenesis. These data indicate that HSF1 is required for the precise expression of Hsp and cytokine genes that is obligatory for maintenance of olfactory neurogenesis in adult mice and suggest that stress-related processes are involved in its maintenance.
Takaki
Eiichi
E
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube 755-8505, Japan.
Fujimoto
Mitsuaki
M
Sugahara
Kazuma
K
Nakahari
Takashi
T
Yonemura
Shigenobu
S
Tanaka
Yasunori
Y
Hayashida
Naoki
N
Inouye
Sachiye
S
Takemoto
Tsuyoshi
T
Yamashita
Hiroshi
H
Nakai
Akira
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016923:Cell Death; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D000076249:Heat Shock Transcription Factors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012903:Smell; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; C484462:Hsf4 protein, mouse; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA; D001973:Bromodeoxyuridine