Sequential perturbations to mouse corticogenesis following in utero maternal immune activation

• Main Authors: Cesar P Canales, Myka L Estes, Karol Cichewicz, Kartik Angara, John Paul Aboubechara, Scott Cameron, Kathryn Prendergast, Linda Su-Feher, Iva Zdilar, Ellie J Kreun, Emma C Connolly, Jin Myeong Seo, Jack B Goon, Kathleen Farrelly, Tyler W Stradleigh, Deborah van der List, Lori Haapanen, Judy Van de Water, Daniel Vogt, A Kimberley McAllister, Alex S Nord
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-03-01
• Series: eLife
• Subjects: MIA; RNA-Seq; transcriptomic; brain development; WGCNA
• Online Access: https://elifesciences.org/articles/60100

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 6 hr 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.