Sequential perturbations to mouse corticogenesis following in utero maternal immune activation
- University of California, Davis, United States
- Michigan State University, United States
Abstract
In utero exposure to maternal immune activation (MIA) is an environmental risk factor for neurodevelopmental and neuropsychiatric disorders. Animal models provide an opportunity to identify mechanisms driving neuropathology associated with MIA. We performed time course transcriptional profiling of mouse cortical development following induced MIA via poly(I:C) injection at E12.5. MIA-driven transcriptional changes were validated via protein analysis, and parallel perturbations to cortical neuroanatomy were identified via imaging. MIA-induced acute upregulation of genes associated with hypoxia, immune signaling, and angiogenesis, by six hours following exposure. This acute response was followed by changes in proliferation, neuronal and glial specification, and cortical lamination that emerged at E14.5 and peaked at E17.5. Decreased numbers of proliferative cells in germinal zones and alterations in neuronal and glial populations were identified in the MIA-exposed cortex. Overall, paired transcriptomic and neuroanatomical characterization revealed a sequence of perturbations to corticogenesis driven by mid-gestational MIA.
Data availability
Sequencing data (raw and gene-count data for RNA-seq) have been deposited in GEO under accession number GSE166376. Available at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166376Data analysis code is available at: https://github.com/NordNeurogenomicsLab/Publications/tree/master/Canales_eLife_2021Detailed DE analysis are included in the manuscript and supporting files (Supplementary files 1-15) and can be visualized using our interactive online browser at: https://nordlab.shinyapps.io/mia_browser/.
Article and author information
Author details
Funding
National Institute of Mental Health (2T32MH073124-16)
- Cesar P Canales
National Institute of Mental Health (5R21MH116681-02)
- Kim McAllister
- Alex S Nord
Brain Research Foundation
- Alex S Nord
The UCD Clinical Translational Science Center
- Kim McAllister
- Alex S Nord
National Institute of General Medical Sciences (GM119831)
- Alex S Nord
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was conducted in compliance with NIH guidelines and approved protocols from the University of California Davis Animal Care and Use Committee (IACUC) protocol #20229
Copyright
© 2021, Canales et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sequential perturbations to mouse corticogenesis following in utero maternal immune activation
eLife 10:e60100.
https://doi.org/10.7554/eLife.60100
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