Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone
Summary: Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventric...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723014353 |
| _version_ | 1797448055728898048 |
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| author | Vivianne Morrison Matthew Houpert Jonathan Trapani Asa Brockman Philip Kingsley Ketaki Katdare Hillary Layden Gabriela Nguena-Jones Alexandra Trevisan Kathleen Maguire-Zeiss Lawrence Marnett Gregory Bix Rebecca Ihrie Bruce Carter |
| author_facet | Vivianne Morrison Matthew Houpert Jonathan Trapani Asa Brockman Philip Kingsley Ketaki Katdare Hillary Layden Gabriela Nguena-Jones Alexandra Trevisan Kathleen Maguire-Zeiss Lawrence Marnett Gregory Bix Rebecca Ihrie Bruce Carter |
| author_sort | Vivianne Morrison |
| collection | DOAJ |
| description | Summary: Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ. |
| first_indexed | 2024-03-09T14:04:50Z |
| format | Article |
| id | doaj.art-7082f82feb184f19a031bfe1b3083d6c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:04:50Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7082f82feb184f19a031bfe1b3083d6c2023-11-30T05:07:12ZengElsevierCell Reports2211-12472023-11-014211113423Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zoneVivianne Morrison0Matthew Houpert1Jonathan Trapani2Asa Brockman3Philip Kingsley4Ketaki Katdare5Hillary Layden6Gabriela Nguena-Jones7Alexandra Trevisan8Kathleen Maguire-Zeiss9Lawrence Marnett10Gregory Bix11Rebecca Ihrie12Bruce Carter13Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA; Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USAVanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Neuroscience, Georgetown University, Washington, DC 20057, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA; A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USACenter for Clinical Neuroscience Research, Tulane University, New Orleans, LA 70118, USADepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA; Corresponding authorSummary: Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ.http://www.sciencedirect.com/science/article/pii/S2211124723014353CP: Neuroscience |
| spellingShingle | Vivianne Morrison Matthew Houpert Jonathan Trapani Asa Brockman Philip Kingsley Ketaki Katdare Hillary Layden Gabriela Nguena-Jones Alexandra Trevisan Kathleen Maguire-Zeiss Lawrence Marnett Gregory Bix Rebecca Ihrie Bruce Carter Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone Cell Reports CP: Neuroscience |
| title | Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone |
| title_full | Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone |
| title_fullStr | Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone |
| title_full_unstemmed | Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone |
| title_short | Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone |
| title_sort | jedi 1 megf12 mediated phagocytosis controls the pro neurogenic properties of microglia in the ventricular subventricular zone |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723014353 |
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