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

• DOI: 10.1083/jcb.200107009
• Publication Date: 2002-07-26T16:46:23Z
• Authors: Ulrich Schweizer; Jennifer Gunnersen; Christoph Karch; Stefan Wiese; Bettina Holtmann; Kiyoshi Takeda; Shizuo Akira; Michael Sendtner
• Keywords: Ciliary neurotrophic factor; Glycoprotein 130; Neurofilament

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