Disrupted in Schizophrenia-1 (DISC1) is a candidate gene for psychiatric disorders and has many roles during brain development. Common DISC1 polymorphisms (variants) are associated with neuropsychiatric phenotypes including altered cognition, brain structure, and function; however, it is unknown how this occurs. Here, we demonstrate using mouse, zebrafish, and human model systems that DISC1 variants are loss of function in Wnt/GSK3β signaling and disrupt brain development. The DISC1 variants A83V, R264Q, and L607F, but not S704C, do not activate Wnt signaling compared with wild-type DISC1 resulting in decreased neural progenitor proliferation. In zebrafish, R264Q and L607F could not rescue DISC1 knockdown-mediated aberrant brain development. Furthermore, human lymphoblast cell lines endogenously expressing R264Q displayed impaired Wnt signaling. Interestingly, S704C inhibited the migration of neurons in the developing neocortex. Our data demonstrate DISC1 variants impair Wnt signaling and brain development and elucidate a possible mechanism for their role in neuropsychiatric phenotypes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387684 | PMC |
| http://dx.doi.org/10.1016/j.neuron.2011.09.030 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deep learning on CT scans to predict checkpoint inhibitor treatment outcomes in advanced melanoma.
Sci Rep
December 2024
Medical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Immune checkpoint inhibitor (ICI) treatment has proven successful for advanced melanoma, but is associated with potentially severe toxicity and high costs. Accurate biomarkers for response are lacking. The present work is the first to investigate the value of deep learning on CT imaging of metastatic lesions for predicting ICI treatment outcomes in advanced melanoma.
View Article and Find Full Text PDFEpidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity.
Nat Commun
December 2024
KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium.
The 2015-2016 Zika virus (ZIKV) outbreak in the Americas revealed the ability of ZIKV from the Asian lineage to cause birth defects, generically called congenital Zika syndrome (CZS). Notwithstanding the long circulation history of Asian ZIKV, no ZIKV-associated CZS cases were reported prior to the outbreaks in French Polynesia (2013) and Brazil (2015). Whether the sudden emergence of CZS resulted from an evolutionary event of Asian ZIKV has remained unclear.
View Article and Find Full Text PDFAlleviating batch effects in cell type deconvolution with SCCAF-D.
Nat Commun
December 2024
GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou, China.
Cell type deconvolution methods can impute cell proportions from bulk transcriptomics data, revealing changes in disease progression or organ development. But benchmarking studies often use simulated bulk data from the same source as the reference, which limits its application scenarios. This study examines batch effects in deconvolution and introduces SCCAF-D, a computational workflow that ensures a Pearson Correlation Coefficient above 0.
View Article and Find Full Text PDFFerritin-Based Supramolecular Assembly Drug Delivery System for Aminated Fullerene Derivatives to Enhance Tumor-Targeted Therapy.
Adv Sci (Weinh)
December 2024
CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
Owing to their attractive antitumor effects, aminated fullerene derivatives are emerging as promising therapeutic drugs for cancer. However, their in vivo applications are severely limited due to cation toxicity. To address this problem, human heavy chain ferritin (HFn), possessing natural biocompatibility is utilized, to develop a novel supramolecular assembly drug delivery system.
View Article and Find Full Text PDFNeurochemical Databases: Purpose and Expectations.
ACS Chem Neurosci
December 2024
University of Bordeaux, CNRS, Institut des Neurosciences Intégratives et Cognitives d'Aquitaine INCIA CNRS UMR5287, F-33000 Bordeaux, France.
The exploration of increasingly specific brain structures and their relationships, in more nuanced ways, has facilitated the generation of databases for gene expression, connectivity, cell morphology, and electrophysiology. However, neurochemistry, the study of neurochemical environment and transmission, has not yet warranted a public database, despite the plethora of data published. From our viewpoint, a neurochemical database is overdue and would allow the field of neurochemistry to develop facilitating, standardization and reference values, reproducibility, resource efficiency, preservation and accessibility of raw data, hypothesis development and exploration, and metadata analysis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!