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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 09, 2021 |
| Title |
A temporal map of maternal immune activation-induced changes reveals a shift in neurodevelopmental timing and perturbed cortical development in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Environmental insults that activate the maternal immune system are potent primers of developmental neuropathology and maternal immune activation (MIA) has emerged as a risk factor for neurodevelopmental and psychiatric disorders. Animal models of MIA provide an opportunity to identify molecular pathways that initiate disease processes and lead to neuropathology and behavioral deficits in offspring. MIA-induced behaviors are accompanied by anatomical and neurochemical alterations in adult offspring that parallel those seen in affected human populations. Methods: We performed transcriptional profiling and neuroanatomical characterization in a time course across mouse embryonic cortical development, following MIA via single injection of the viral mimic polyinosinic:polycytidylic acid (polyI:C) at E12.5. Transcriptional changes identified in the cortex of MIA offspring at E17.5 were validated and mapped to cortical neuroanatomy and cell types via protein analysis and immunohistochemistry. Results: MIA induced strong transcriptomic signatures, including induction of genes associated with hypoxia, immune signaling, and angiogenesis. The acute response identified 6h after the MIA insult was followed by changes in proliferation, neuronal and glial differentiation, and cortical lamination that emerged at E14.5 and peaked at E17.5. Decreased numbers of proliferative cell types in germinal zones and alterations in neuronal and glial cell types across cortical lamina were identified in the MIA-exposed cortex. Conclusions: MIA-induced transcriptomic signatures in fetal offspring overlap significantly with perturbations identified in neurodevelopmental disorders (NDDs), and provide novel insights into alterations in molecular and developmental timing processes linking MIA and neuropathology, potentially revealing new targets for development of novel approaches for earlier diagnosis and treatment of these disorders.
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| Overall design |
Timecourse transcriptomics signatures in a developing mouse cortex following maternal immune activation (MIA) via polyinosinic:polycytidylic acid (polyI:C) at E12.5, E 14.5, E17.5, and at P0
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| Contributor(s) |
Canales CP, Estes ML, Cichewicz K, Angara K, Aboubechara JP, Cameron S, Prendergast K, Su-Feher L, Zdilar I, Kreun EJ, Connolly EC, Seo JM, Goon JB, Farrelly K, Stradleigh T, van der List D, Haapanen L, Van de Water J, Vogt D, McAllister K, Nord AS |
| Citation(s) |
33666173 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R21 MH116681 |
Prenatal brain development following maternal immune activation |
UNIVERSITY OF CALIFORNIA DAVIS |
Alexander Nord |
| R35 GM119831 |
Functional Elucidation of the Sequence-Encoded Regulatory Activity of Enhancers in Vivo in the Brain |
UNIVERSITY OF CALIFORNIA DAVIS |
Alexander Nord |
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| Submission date |
Feb 08, 2021 |
| Last update date |
Apr 06, 2021 |
| Contact name |
Alexander Star Nord |
| E-mail(s) |
asnord@ucdavis.edu
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| Organization name |
University of California Davis
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| Department |
Center for Neuroscience
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| Lab |
Nord Neurogenomics lab
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| Street address |
1544 Newton Court
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95618 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (74)
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| Relations |
| BioProject |
PRJNA700641 |
| SRA |
SRP305337 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166376_Gene_counts.csv.gz |
2.3 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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