title: Microglia development follows a stepwise program to regulate brain homeostasis.
abstract: Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain--early, pre-, and adult microglia--which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Matcovitch-Natan
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Winter
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Giladi
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Robert-Rössle-Straß 10, 13125 Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vargas Aguilar
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Spinrad
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Sarrazin
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Ben-Yehuda
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Zelada González
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Perrin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren-Shaul
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Gury
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Lara-Astaiso
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Bahar Halpern
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Kuti
authors.initials: K
authors.lastname: Baruch
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Deczkowska
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Erika
authors.initials: E
authors.lastname: Lorenzo-Vivas
authors.affiliation: Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Robert-Rössle-Straß 10, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Sieweke
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000196:embryology / Q000276:immunology; D001921:Brain / Q000196:embryology* / Q000276:immunology; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D042421:Histone Code; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D007109:Immunity / Q000235:genetics; D051258:MafB Transcription Factor / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology* / Q000276:immunology; D022423:Myeloid Cells / Q000166:cytology; D055495:Neurogenesis / Q000235:genetics / Q000276:immunology*; D059010:Single-Cell Analysis
chemical_list: D002843:Chromatin; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse