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Papers In Press, published online ahead of print November 23, 2005
J. Biol. Chem, 10.1074/jbc.M506911200
Submitted on June 24, 2005
Accepted on November 22, 2005

Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice

Eiichi Takaki, Mitsuaki Fujimoto, Kazuma Sugahara, Takashi Nakahari, Shigenobu Yonemura, Yasunori Tanaka, Naoki Hayashida, Sachiye Inouye, Tsuyoshi Takemoto, Hiroshi Yamashita, and Akira Nakai

Department of Biochemistry and Molecular Biology, Yamanuchi University School of Medicine, Ube 755-8505

Corresponding Author: anakai{at}yamaguchi-u.ac.jp

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 post-natal 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 the olfactory neurogenesis in the adult mice, and suggest that stress-related processes are involved in its maintenance.


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