ArticlePloS one2012
Abnormal levels of Gadd45alpha in developing neocortex impair neurite outgrowth.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Folate Receptor Alpha (FRα) and the Developing Brain: From Molecular Function to Neurodevelopmental Outcomes.Molecular neurobiology · 2026Review
- Ventral Hippocampal CA1 GADD45B Regulates Susceptibility to Social Stress by Influencing NMDA Receptor-Mediated Synaptic Plasticity.Neuroscience bulletin · 2025Article
- MAP3K4 kinase action and dual role in cancer.Discover oncology · 2024Review
- Identification of potential crucial genes and therapeutic targets for epilepsy.European journal of medical research · 2024Article
- Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.Frontiers in neuroscience · 2024Review
- Induced Coma, Death, and Organ Transplantation: A Physiologic, Genetic, and Theological Perspective.International journal of molecular sciences · 2023Review
- Gadd45 in Neuronal Development, Function, and Injury.Advances in experimental medicine and biology · 2022Review
- A Mouse Brain-based Multi-omics Integrative Approach Reveals Potential Blood Biomarkers for Ischemic Stroke.Molecular & cellular proteomics : MCP · 2020Article
- Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress.Science advances · 2020Article
- Global gene expression analysis combined with a genomics approach for the identification of signal transduction networks involved in postnatal mouse myocardial proliferation and development.International journal of molecular medicine · 2018Article
- Behavior-linked FoxP2 regulation enables zebra finch vocal learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.PloS one · 2014Article
- Arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways.Frontiers in psychiatry · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To better understand the short and long-term effects of stress on the developing cerebral cortex, it is necessary to understand how early stress response genes protect or permanently alter cells. One family of highly conserved, stress response genes is the growth arrest and DNA damage-45 (Gadd45) genes. The expression of these genes is induced by a host of genotoxic, drug, and environmental stressors. Here we examined the impact of altering the expression of Gadd45alpha (Gadd45a), a member of the Gadd45 protein family that is expressed throughout the developing cortices of mice and humans. To manipulate levels of Gadd45a protein in developing mouse cortex, we electroporated cDNA plasmids encoding either Gadd45a or Gadd45a shRNA to either overexpress or knockdown Gadd45a levels in the developing cortices of mice, respectively. The effects of these manipulations were assessed by examining the fates and morphologies of the labeled neurons. Gadd45a overexpression both in vitro and in vivo significantly impaired the morphology of neurons, decreasing neurite complexity, inducing soma hypertrophy and increasing cell death. Knockdown of Gadd45a partially inhibited neuronal migration and reduced neurite complexity, an effect that was reversed in the presence of an shRNA-resistant Gadd45a. Finally, we found that shRNA against MEKK4, a direct target of Gadd45a, also stunted neurite outgrowth. Our findings suggest that the expression of Gadd45a in normal, developing brain is tightly regulated and that treatments or environmental stimuli that alter its expression could produce significant changes in neuronal circuitry development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.