Conditional gene ablation of Stat3 reveals differential signalling requirements for survival of motoneurons during development and after nerve injury in the adult.
Project management at the University of Würzburg:
Members of the CNTF gene family are potent survival factors for motoneurons. These factors act via receptor complexes involving gp130 and LIFR-beta. Intracellular signalling pathways which are activated by these receptor complexes include the phosphorylation of Stat3. We have generated mice in which Stat3 is specifically deleted in embryonic and postnatal motoneurons. In these mice, loss of motoneurons is not enhanced during the embryonic period of naturally occuring cell death. In contrast, motoneuron survival is significantly reduced after facial nerve lesion in the adult. Additional experiments revealed that Stat3 is essential for upregulation of Reg-2 andBcl-xl in lesioned motoneurons. Our data show that Stat3 activation is essential for motoneuron survival after nerve lesion but not during embryonic development, indicating that signalling requirements for motoneuron survival change during maturation.
Projekt period: from 01.1999 to 12.2002