PUBLICATION
Type-I-interferon-responsive microglia shape cortical development and behavior
- Authors
- Escoubas, C.C., Dorman, L.C., Nguyen, P.T., Lagares-Linares, C., Nakajo, H., Anderson, S.R., Barron, J.J., Wade, S.D., Cuevas, B., Vainchtein, I.D., Silva, N.J., Guajardo, R., Xiao, Y., Lidsky, P.V., Wang, E.Y., Rivera, B.M., Taloma, S.E., Kim, D.K., Kaminskaya, E., Nakao-Inoue, H., Schwer, B., Arnold, T.D., Molofsky, A.B., Condello, C., Andino, R., Nowakowski, T.J., Molofsky, A.V.
- ID
- ZDB-PUB-240316-2
- Date
- 2024
- Source
- Cell 187(8): 1936-1954.e24 (Journal)
- Registered Authors
- Molofsky, Anna Victoria
- Keywords
- cortical development, microglia, neuroimmunity, phagocytosis, somatosensory cortex, tactile hypersensitivity, type I interferon
- MeSH Terms
-
- Animals
- Interferon Type I*/metabolism
- Brain*/cytology
- Brain*/growth & development
- Zebrafish
- Mice
- Microglia*/metabolism
- Neurons/metabolism
- PubMed
- 38490196 Full text @ Cell
Citation
Escoubas, C.C., Dorman, L.C., Nguyen, P.T., Lagares-Linares, C., Nakajo, H., Anderson, S.R., Barron, J.J., Wade, S.D., Cuevas, B., Vainchtein, I.D., Silva, N.J., Guajardo, R., Xiao, Y., Lidsky, P.V., Wang, E.Y., Rivera, B.M., Taloma, S.E., Kim, D.K., Kaminskaya, E., Nakao-Inoue, H., Schwer, B., Arnold, T.D., Molofsky, A.B., Condello, C., Andino, R., Nowakowski, T.J., Molofsky, A.V. (2024) Type-I-interferon-responsive microglia shape cortical development and behavior. Cell. 187(8):1936-1954.e24.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping