Neuronal death in Drosophila triggered by GAL4 accumulation.
The GAL4/UAS system has been extensively employed in Drosophila to control gene expression in defined spatial patterns. More recently this system has been successfully applied to express genes involved in neurodegeneration to model various diseases in the fruit fly. We used transgenic lines expressi...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1826267539284426752 |
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| author | Rezával, C Werbajh, S Ceriani, M |
| author_facet | Rezával, C Werbajh, S Ceriani, M |
| author_sort | Rezával, C |
| collection | OXFORD |
| description | The GAL4/UAS system has been extensively employed in Drosophila to control gene expression in defined spatial patterns. More recently this system has been successfully applied to express genes involved in neurodegeneration to model various diseases in the fruit fly. We used transgenic lines expressing different levels of GAL4 in a particular subset of neurons involved in the control of rhythmic behaviour, so that its impact on neuronal physiology would result in altered locomotor activity, which could be readily assessed. We observed a striking correlation between gal4 dosage and behavioural defects associated with apoptotic neuronal loss in the specific GAL4-expressing neurons. Increased gal4 dosage correlated with accumulation of insoluble GAL4, suggesting that the cascade of events leading to apoptosis might be triggered by protein deposits of either GAL4 or protein intermediates. Behavioural defects were rescued by expression of hsp70, a classic chaperone that also interferes with cell death pathways. In agreement with the latter, the viral caspase inhibitor p35 also rescued GAL4-induced behavioural defects. Our observations demonstrate the intrinsic effects of GAL4 deregulation on neuronal viability and suggest that an excess of GAL4 might enhance neuronal deficits observed in models of neurodegeneration. |
| first_indexed | 2024-03-06T20:55:45Z |
| format | Journal article |
| id | oxford-uuid:3931414d-d941-405c-ace5-2e096d5769a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:55:45Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:3931414d-d941-405c-ace5-2e096d5769a22022-03-26T13:54:09ZNeuronal death in Drosophila triggered by GAL4 accumulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3931414d-d941-405c-ace5-2e096d5769a2EnglishSymplectic Elements at Oxford2007Rezával, CWerbajh, SCeriani, MThe GAL4/UAS system has been extensively employed in Drosophila to control gene expression in defined spatial patterns. More recently this system has been successfully applied to express genes involved in neurodegeneration to model various diseases in the fruit fly. We used transgenic lines expressing different levels of GAL4 in a particular subset of neurons involved in the control of rhythmic behaviour, so that its impact on neuronal physiology would result in altered locomotor activity, which could be readily assessed. We observed a striking correlation between gal4 dosage and behavioural defects associated with apoptotic neuronal loss in the specific GAL4-expressing neurons. Increased gal4 dosage correlated with accumulation of insoluble GAL4, suggesting that the cascade of events leading to apoptosis might be triggered by protein deposits of either GAL4 or protein intermediates. Behavioural defects were rescued by expression of hsp70, a classic chaperone that also interferes with cell death pathways. In agreement with the latter, the viral caspase inhibitor p35 also rescued GAL4-induced behavioural defects. Our observations demonstrate the intrinsic effects of GAL4 deregulation on neuronal viability and suggest that an excess of GAL4 might enhance neuronal deficits observed in models of neurodegeneration. |
| spellingShingle | Rezával, C Werbajh, S Ceriani, M Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title | Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title_full | Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title_fullStr | Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title_full_unstemmed | Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title_short | Neuronal death in Drosophila triggered by GAL4 accumulation. |
| title_sort | neuronal death in drosophila triggered by gal4 accumulation |
| work_keys_str_mv | AT rezavalc neuronaldeathindrosophilatriggeredbygal4accumulation AT werbajhs neuronaldeathindrosophilatriggeredbygal4accumulation AT cerianim neuronaldeathindrosophilatriggeredbygal4accumulation |