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Leukemia Inhibitory Factor Is a Key Signal for Injury-Induced Neurogenesis in the Adult Mouse Olfactory Epithelium

Bauer, S. and Rasika, S. and Han, Jing and Mauduit, C. and Raccurt, M. and Morel, G. and Jourdan, F. and Benahmed, M. and Moyse, E. and Patterson, P. H. (2003) Leukemia Inhibitory Factor Is a Key Signal for Injury-Induced Neurogenesis in the Adult Mouse Olfactory Epithelium. Journal of Neuroscience, 23 (5). pp. 1792-1803. ISSN 0270-6474. PMCID PMC6741956. doi:10.1523/JNEUROSCI.23-05-01792.2003.

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The mammalian olfactory epithelium (OE) is composed of primary olfactory sensory neurons (OSNs) that are renewed throughout adulthood by local, restricted neuronal progenitor cells. The molecular signals that control this neurogenesis in vivo are unknown. Using olfactory bulb ablation (OBX) in adult mice to trigger synchronous mitotic stimulation of neuronal progenitors in the OE, we show the in vivo involvement of a cytokine in the cellular events leading to the regeneration of the OE. We find that, of many potential mitogenic signals, only leukemia inhibitory factor (LIF) is induced before the onset of neuronal progenitor proliferation. The rise in LIF mRNA expression peaks at 8 hr after OBX, and in situ RT-PCR and immunocytochemistry indicate that LIF is upregulated, in part, in the injured neurons themselves. This rise in LIF is necessary for injury-induced neurogenesis, as OBX in the LIF knock-out mouse fails to stimulate cell proliferation in the OE. Moreover, delivery of exogenous LIF to the intact adult OE using an adenoviral vector stimulates BrdU labeling in the apical OE. Taken together, these results suggest that injured OSNs release LIF as a stimulus to initiate their own replacement.

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Additional Information:© 2003 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Sept. 1, 2002; revised Dec. 4, 2002; accepted Dec. 13, 2002. This study was supported by Association pour la Recherche sur le Cancer Grant 1377 (E.M.) and by Fondation de Gérontologie Française and Société de Biologie du Vieillissement (S.B.), as well as by the National Institute of Neurological Disorders and Stroke (P.H.P.). We thank Doreen McDowell and Catherine Berthet for excellent administrative assistance. We thank Dr. Emmanuelle Danty for the OMP cDNA plasmid.
Funding AgencyGrant Number
Association pour la Recherche sur le Cancer1377
Fondation de Gérontologie FrançaiseUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Société de Biologie du VieillissementUNSPECIFIED
Subject Keywords:LIF; gp130; IL-6; BMP; stem cells; olfaction
Issue or Number:5
PubMed Central ID:PMC6741956
Record Number:CaltechAUTHORS:20160210-150617968
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Official Citation:Leukemia Inhibitory Factor Is a Key Signal for Injury-Induced Neurogenesis in the Adult Mouse Olfactory Epithelium S. Bauer, S. Rasika, Jing Han, C. Mauduit, M. Raccurt, G. Morel, F. Jourdan, M. Benahmed, E. Moyse, and P. H. Patterson The Journal of Neuroscience, 1 March 2003, 23(5):1792-1803
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64389
Deposited By: Ruth Sustaita
Deposited On:10 Feb 2016 23:44
Last Modified:10 Nov 2021 23:30

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