Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection
Accurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cel...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1274174/full |
| _version_ | 1827318262190309376 |
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| author | Maria Letizia Potenza Stefan Blankvoort Miguel M. Carvalho Joachim S. Grimstvedt Valentina Di Maria Kristian Moan Rajeevkumar Raveendran Nair Marcus S. Flatset Qiangwei Zhang Laurent F. Thomas Francois P. Pauzin Francois P. Pauzin Rodolfo Da Silva Mazzarini Baldinotti Rodolfo Da Silva Mazzarini Baldinotti Giulia Quattrocolo Giulia Quattrocolo Clive R. Bramham Clive R. Bramham Pål Sætrom Pål Sætrom Pål Sætrom Menno P. Witter Menno P. Witter Clifford G. Kentros Clifford G. Kentros Clifford G. Kentros |
| author_facet | Maria Letizia Potenza Stefan Blankvoort Miguel M. Carvalho Joachim S. Grimstvedt Valentina Di Maria Kristian Moan Rajeevkumar Raveendran Nair Marcus S. Flatset Qiangwei Zhang Laurent F. Thomas Francois P. Pauzin Francois P. Pauzin Rodolfo Da Silva Mazzarini Baldinotti Rodolfo Da Silva Mazzarini Baldinotti Giulia Quattrocolo Giulia Quattrocolo Clive R. Bramham Clive R. Bramham Pål Sætrom Pål Sætrom Pål Sætrom Menno P. Witter Menno P. Witter Clifford G. Kentros Clifford G. Kentros Clifford G. Kentros |
| author_sort | Maria Letizia Potenza |
| collection | DOAJ |
| description | Accurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cell-type. We recently used enhancers, the subcomponents of the transcriptional apparatus which tell promoters when and where to express, combined with heterologous minimal promoters to increase specificity of transgene expression, an approach we call Enhancer-Driven Gene Expression (EDGE). As we discuss, EDGE is a marked improvement in specificity over native promoters, but still requires careful anatomical analysis to avoid off-target effects. In this study we present a more complete set of genomic markers from the mouse brain and characterize a novel EDGE viral vector capable of specifically driving expression in distinct subtypes of hippocampal neurons, even though it can express in other cell-types elsewhere. The advent of cell-type specific viral tools in wild-type animals provides a powerful strategy for neural circuit investigation and holds promise for studies using animal models for which transgenic tools are not available. |
| first_indexed | 2024-04-24T23:56:09Z |
| format | Article |
| id | doaj.art-75c3588560e24daa9e9cd2efe9d93a58 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-24T23:56:09Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-75c3588560e24daa9e9cd2efe9d93a582024-03-14T12:51:29ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-03-011810.3389/fnins.2024.12741741274174Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injectionMaria Letizia Potenza0Stefan Blankvoort1Miguel M. Carvalho2Joachim S. Grimstvedt3Valentina Di Maria4Kristian Moan5Rajeevkumar Raveendran Nair6Marcus S. Flatset7Qiangwei Zhang8Laurent F. Thomas9Francois P. Pauzin10Francois P. Pauzin11Rodolfo Da Silva Mazzarini Baldinotti12Rodolfo Da Silva Mazzarini Baldinotti13Giulia Quattrocolo14Giulia Quattrocolo15Clive R. Bramham16Clive R. Bramham17Pål Sætrom18Pål Sætrom19Pål Sætrom20Menno P. Witter21Menno P. Witter22Clifford G. Kentros23Clifford G. Kentros24Clifford G. Kentros25Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayBioCore Bioinformatics Core Facility, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayDepartment of Biomedicine, University of Bergen, Bergen, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayDepartment of Biomedicine, University of Bergen, Bergen, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayDepartment of Biomedicine, University of Bergen, Bergen, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayBioCore Bioinformatics Core Facility, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayDepartment of Computer Science, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayKavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, NTNU, Trondheim, NorwayMohn Research Center for the Brain, University of Bergen, Bergen, NorwayInstitute of Neuroscience, University of Oregon, Eugene, OR, United StatesAccurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cell-type. We recently used enhancers, the subcomponents of the transcriptional apparatus which tell promoters when and where to express, combined with heterologous minimal promoters to increase specificity of transgene expression, an approach we call Enhancer-Driven Gene Expression (EDGE). As we discuss, EDGE is a marked improvement in specificity over native promoters, but still requires careful anatomical analysis to avoid off-target effects. In this study we present a more complete set of genomic markers from the mouse brain and characterize a novel EDGE viral vector capable of specifically driving expression in distinct subtypes of hippocampal neurons, even though it can express in other cell-types elsewhere. The advent of cell-type specific viral tools in wild-type animals provides a powerful strategy for neural circuit investigation and holds promise for studies using animal models for which transgenic tools are not available.https://www.frontiersin.org/articles/10.3389/fnins.2024.1274174/fullrAAVsdentate gyrusgenetic toolchromatin immunoprecipitationstereotaxic injection |
| spellingShingle | Maria Letizia Potenza Stefan Blankvoort Miguel M. Carvalho Joachim S. Grimstvedt Valentina Di Maria Kristian Moan Rajeevkumar Raveendran Nair Marcus S. Flatset Qiangwei Zhang Laurent F. Thomas Francois P. Pauzin Francois P. Pauzin Rodolfo Da Silva Mazzarini Baldinotti Rodolfo Da Silva Mazzarini Baldinotti Giulia Quattrocolo Giulia Quattrocolo Clive R. Bramham Clive R. Bramham Pål Sætrom Pål Sætrom Pål Sætrom Menno P. Witter Menno P. Witter Clifford G. Kentros Clifford G. Kentros Clifford G. Kentros Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection Frontiers in Neuroscience rAAVs dentate gyrus genetic tool chromatin immunoprecipitation stereotaxic injection |
| title | Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection |
| title_full | Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection |
| title_fullStr | Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection |
| title_full_unstemmed | Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection |
| title_short | Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection |
| title_sort | generation of an enhancer driven gene expression viral tool specific to dentate granule cell types through direct hippocampal injection |
| topic | rAAVs dentate gyrus genetic tool chromatin immunoprecipitation stereotaxic injection |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1274174/full |
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