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© The Rockefeller University Press, 0021-9525/2002/1/287 $5.00
The Journal of Cell Biology, Volume 156, Number 2, January 21, 2002 287-298

Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult

¹ Institute for Clinical Neurobiology, University of Würzburg, 97080 Würzburg, Germany
² Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan

Address correspondence to Michael Sendtner, Institute for Clinical Neurobiology, Josef Schneider Strasse 11, 97080 Würzburg, Germany. Tel.: (49) 931-201-5771. Fax: (49) 931-201-2697. E-mail: sendtner{at}mail.uni-wuerzburg.de

Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These factors act via receptor complexes involving gp130 and LIFR-ß and ligand binding leads to activation of various signaling pathways, including phosphorylation of Stat3. The role of Stat3 in neuronal survival was investigated in mice by Cre-mediated gene ablation in motoneurons. Cre is expressed under the neurofilament light chain (NF-L) promoter, starting around E12 when these neurons become dependent on neurotrophic support. Loss of motoneurons during the embryonic period of naturally occurring cell death is not enhanced in NF-L–Cre; Stat3^flox/KO mice although motoneurons isolated from these mice need higher concentrations of CNTF for maximal survival in culture. In contrast, motoneuron survival is significantly reduced after facial nerve lesion in the adult. These neurons, however, can be rescued by the addition of neurotrophic factors, including CNTF. Stat3 is essential for upregulation of Reg-2 and Bcl-xl expression in lesioned motoneurons. Our data show that Stat3 activation plays an essential role for motoneuron survival after nerve lesion in postnatal life but not during embryonic development, indicating that signaling requirements for motoneuron survival change during maturation.

Key Words: CNTF; axotomy; lesion; bcl-xl; reg-2

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