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Type-I-interferon-responsive microglia shape cortical development and behavior.
Escoubas, Caroline C; Dorman, Leah C; Nguyen, Phi T; Lagares-Linares, Christian; Nakajo, Haruna; Anderson, Sarah R; Barron, Jerika J; Wade, Sarah D; Cuevas, Beatriz; Vainchtein, Ilia D; Silva, Nicholas J; Guajardo, Ricardo; Xiao, Yinghong; Lidsky, Peter V; Wang, Ellen Y; Rivera, Brianna M; Taloma, Sunrae E; Kim, Dong Kyu; Kaminskaya, Elizaveta; Nakao-Inoue, Hiromi; Schwer, Bjoern; Arnold, Thomas D; Molofsky, Ari B; Condello, Carlo; Andino, Raul; Nowakowski, Tomasz J; Molofsky, Anna V.
Afiliação
  • Escoubas CC; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Dorman LC; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Nguyen PT; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Lagares-Linares C; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Nakajo H; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Anderson SR; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Barron JJ; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Wade SD; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Cuevas B; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Vainchtein ID; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Silva NJ; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Guajardo R; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Medical Scientist Training Program, Univer
  • Xiao Y; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Lidsky PV; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Wang EY; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; UCSF SRTP program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Rivera BM; Institute for Neurodegenerative Diseases/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Taloma SE; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kim DK; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kaminskaya E; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Nakao-Inoue H; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Schwer B; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurological
  • Arnold TD; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Molofsky AB; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Condello C; Institute for Neurodegenerative Diseases/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Andino R; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Nowakowski TJ; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurological
  • Molofsky AV; Departments of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Eli and Edythe Broad Center
Cell ; 187(8): 1936-1954.e24, 2024 Apr 11.
Article em En | MEDLINE | ID: mdl-38490196
ABSTRACT
Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Interferon Tipo I / Microglia Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Interferon Tipo I / Microglia Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos