Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types
Short cell-type specific promoter sequences are important for targeted gene therapy and studies of brain circuitry. We report on the ability of short promoter sequences to drive fluorescent protein expression in specific types of mammalian cortical inhibitory neurons using adeno-associated virus (AA...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2009-11-01
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| Series: | Frontiers in Neural Circuits |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/neuro.04.019.2009/full |
| _version_ | 1817971286692855808 |
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| author | Jason L Nathanson Jason L Nathanson Roberto Jappelli Eric D Scheeff Gerard Manning Kunihiko Obata Sydney Brenner Edward M Callaway |
| author_facet | Jason L Nathanson Jason L Nathanson Roberto Jappelli Eric D Scheeff Gerard Manning Kunihiko Obata Sydney Brenner Edward M Callaway |
| author_sort | Jason L Nathanson |
| collection | DOAJ |
| description | Short cell-type specific promoter sequences are important for targeted gene therapy and studies of brain circuitry. We report on the ability of short promoter sequences to drive fluorescent protein expression in specific types of mammalian cortical inhibitory neurons using adeno-associated virus (AAV) and lentivirus (LV) vectors. We tested many gene regulatory sequences derived from fugu (Takifugu rubripes), mouse, human, and synthetic composite regulatory elements. All fugu compact promoters expressed in mouse cortex, with only the somatostatin (SST) and the neuropeptide Y (NPY) promoters largely restricting expression to GABAergic neurons. However these promoters did not control expression in inhibitory cells in a subtype specific manner. We also tested mammalian promoter sequences derived from genes putatively coexpressed or coregulated within three major inhibitory interneuron classes (PV, SST, VIP). In contrast to the fugu promoters, many of the mammalian sequences failed to express, and only the promoter from gene A930038C07Rik conferred restricted expression, although as in the case of the fugu sequences, this too was not inhibitory neuron subtype specific. Lastly and more promisingly, a synthetic sequence consisting of a composite regulatory element assembled with PAX6 E1.1 binding sites, NRSE and a minimal CMV promoter showed markedly restricted expression to a small subset of mostly inhibitory neurons, but whose commonalities are unknown. |
| first_indexed | 2024-04-13T20:44:51Z |
| format | Article |
| id | doaj.art-d51eb07e87f34bc8a1b1eaee02b2f2e4 |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-04-13T20:44:51Z |
| publishDate | 2009-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-d51eb07e87f34bc8a1b1eaee02b2f2e42022-12-22T02:30:44ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102009-11-01310.3389/neuro.04.019.2009775Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-typesJason L Nathanson0Jason L Nathanson1Roberto Jappelli2Eric D Scheeff3Gerard Manning4Kunihiko Obata5Sydney Brenner6Edward M Callaway7Salk Institute for Biological StudiesUniversity of California, San DiegoSalk Institute for Biological StudiesSalk Institute for Biological StudiesSalk Institute for Biological StudiesNeuronal Network Mechanisms Research Group, RIKEN Brain Science InstituteSalk Institute for Biological StudiesSalk Institute for Biological StudiesShort cell-type specific promoter sequences are important for targeted gene therapy and studies of brain circuitry. We report on the ability of short promoter sequences to drive fluorescent protein expression in specific types of mammalian cortical inhibitory neurons using adeno-associated virus (AAV) and lentivirus (LV) vectors. We tested many gene regulatory sequences derived from fugu (Takifugu rubripes), mouse, human, and synthetic composite regulatory elements. All fugu compact promoters expressed in mouse cortex, with only the somatostatin (SST) and the neuropeptide Y (NPY) promoters largely restricting expression to GABAergic neurons. However these promoters did not control expression in inhibitory cells in a subtype specific manner. We also tested mammalian promoter sequences derived from genes putatively coexpressed or coregulated within three major inhibitory interneuron classes (PV, SST, VIP). In contrast to the fugu promoters, many of the mammalian sequences failed to express, and only the promoter from gene A930038C07Rik conferred restricted expression, although as in the case of the fugu sequences, this too was not inhibitory neuron subtype specific. Lastly and more promisingly, a synthetic sequence consisting of a composite regulatory element assembled with PAX6 E1.1 binding sites, NRSE and a minimal CMV promoter showed markedly restricted expression to a small subset of mostly inhibitory neurons, but whose commonalities are unknown.http://journal.frontiersin.org/Journal/10.3389/neuro.04.019.2009/fulltranscription factorCortexViral vectorPromoterfuguinhibitory interneuron |
| spellingShingle | Jason L Nathanson Jason L Nathanson Roberto Jappelli Eric D Scheeff Gerard Manning Kunihiko Obata Sydney Brenner Edward M Callaway Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types Frontiers in Neural Circuits transcription factor Cortex Viral vector Promoter fugu inhibitory interneuron |
| title | Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types |
| title_full | Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types |
| title_fullStr | Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types |
| title_full_unstemmed | Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types |
| title_short | Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types |
| title_sort | short promoters in viral vectors drive selective expression in mammalian inhibitory neurons but do not restrict activity to specific inhibitory cell types |
| topic | transcription factor Cortex Viral vector Promoter fugu inhibitory interneuron |
| url | http://journal.frontiersin.org/Journal/10.3389/neuro.04.019.2009/full |
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