Article
- The EMBO Journal (2006) 25, 752 - 762
- doi:10.1038/sj.emboj.7600988
Published online: 9 February 2006
Subject Categories:
Neuronal survival depends on EGFR signaling in cortical but not midbrain astrocytes
Bettina Wagner1,a, Anuradha Natarajan1, Sabine Grünaug1, Renate Kroismayr1, Erwin F Wagner2 and Maria Sibilia1
- Department of Dermatology/DIAID, Medical University of Vienna, Vienna Competence Center (VCC), Vienna, Austria
- Research Institute of Molecular Pathology (IMP), Vienna, Austria
Correspondence to:
Maria Sibilia, Department of Dermatology DIAID/VCC, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria. Tel.: +43 1 40160 63011; Fax: +43 1 40160 963005; E-mail: maria.sibilia@meduniwien.ac.at
aPresent address: APEIRON BIOLOGICS, Brunnerstrasse 59, 1230 Vienna, Austria
Received 16 August 2005; Accepted 13 January 2006
Abstract
Mice lacking epidermal growth factor receptor (EGFR) develop a neurodegeneration of unknown etiology affecting exclusively the frontal cortex and olfactory bulbs. Here, we show that EGFR signaling controls cortical degeneration by regulating cortical astrocyte apoptosis. Whereas EGFR-/- midbrain astrocytes are unaffected, mutant cortical astrocytes display increased apoptosis mediated by an Akt-caspase-dependent mechanism and are unable to support neuronal survival. The expression of many neurotrophic factors is unaltered in EGFR-/- cortical astrocytes suggesting that neuronal loss occurs as a consequence of increased astrocyte apoptosis rather than impaired secretion of trophic factors. Neuron-specific expression of activated Ras can compensate for the deficiency of EGFR-/- cortical astrocytes and prevent neuronal death. These results identify two functionally distinct astrocyte populations, which differentially depend on EGFR signaling for their survival and also for their ability to support neuronal survival. These spatial differences in astrocyte composition provide a mechanism for the region-specific neurodegeneration in EGFR-/- mice.
Keywords:
- cortical astrocytes,
- epidermal growth factor receptor,
- knockout mice,
- midbrain astrocytes,
- neurodegeneration
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