Abnormal neurodevelopment, neurosignaling and behaviour in Npas3-deficient mice
Abstract
Npas3 is a member of the bHLH-PAS superfamily of transcription factors that is expressed broadly in the developing neuroepithelium. To study the function of this gene, mice deficient in Npas3 were generated and characterized. Npas3-/- mice were growth-retarded and exhibited developmental brain abnormalities that included a reduction in size of the anterior hippocampus, hypoplasia of the corpus callosum and enlargement of the ventricles. A number of behavioural abnormalities were identified in Npas3-/- mice including locomotor hyperactivity, subtle gait defects, impairment of prepulse inhibition of acoustic startle, deficit in recognition memory and altered anxiety-related responses. Characterization of neurosignaling pathways using several pharmacological agents revealed dysfunctional glutamate, dopamine and serotonin neurotransmitter signaling. Consistent with these findings, we identified a significant alteration in cortical PSD-95 expression, a PDZ-containing protein that has been shown to be involved in postsynaptic signal transduction. Together, our observations indicate an important role for Npas3 in controlling normal brain development and neurosignaling pathways.
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Npas3 plays an important role during brain development, specifically in the control of neurosignaling pathways, and is involved in astrogenesis.
“Analysis of Npas3 deficient mice (Npas3−/−) showed that this protein plays an important role during brain development, specifically in the control of neurosignaling pathways (Erbel-Sieler et al. 2004; Brunskill et al. 2005), and it was also involved in astrogenesis (Li et al. 2022).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Brunskill et al. 2005
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- Authors
- Brunskill, E. W., Ehrman, L. A., Williams, M. T., Klanke, J., Hammer, D., Schaefer, T. L., Sah, R., Il, G. W. D., Potter, S. S., & Vorhees, C. V.
- Affiliations
- University of Cincinnati (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Brunskill, Eric W.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-09
- Volume
- 22
- Issue
- 6
- Pages
- 1265-1276
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1566594410
- Cited by
- 84
- References
- 54
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL58010, R01HL058010)
- National Institute on Drug Abuse (DA14269, K01DA014269, R01DA006733, DA06733)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061916, DK61916)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- NPAS3, bHLH-PAS transcription factors, brain development, corpus callosum hypoplasia, ventriculomegaly, locomotor hyperactivity, prepulse inhibition, recognition memory, anxiety, glutamate signaling, dopamine signaling, serotonin signaling, PSD-95, neurodevelopmental disorders
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Behavior, Animal, Brain, Postural Balance, Magnetic Resonance Imaging, Membrane Proteins, Motor Activity, Nervous System, Signal Transduction, Mice, Knockout, Neurotransmitter Agents, Reverse Transcriptase Polymerase Chain Reaction, Gait Ataxia, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases, Basic Helix-Loop-Helix Proteins
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