Related Experiment Video
Updated: May 27, 2026
08:44
Generation of Topically Transgenic Rats by In utero Electroporation and In vivo Bioluminescence Screening
Published on: September 24, 2013
Common DISC1 polymorphisms disrupt Wnt/GSK3β signaling and brain development.
Karun K Singh1, Gianluca De Rienzo, Laurel Drane
1Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Neuron
|November 22, 2011
Summary
Common variants of the Disrupted in Schizophrenia-1 (DISC1) gene impair Wnt signaling and disrupt brain development, potentially explaining their link to neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Disrupted in Schizophrenia-1 (DISC1) is a key gene implicated in psychiatric disorders.
- DISC1 plays crucial roles in brain development, but the mechanisms linking its variants to phenotypes are unclear.
Purpose of the Study:
- To investigate how common DISC1 variants affect Wnt/GSK3β signaling and brain development.
- To elucidate the functional consequences of specific DISC1 variants (A83V, R264Q, L607F, S704C).
Main Methods:
- Utilized mouse, zebrafish, and human lymphoblast cell line models.
- Assessed Wnt signaling activation, neural progenitor proliferation, and neuron migration.
- Examined the rescue capabilities of DISC1 variants in zebrafish models.
Main Results:
- DISC1 variants A83V, R264Q, and L607F showed loss-of-function in Wnt signaling compared to wild-type DISC1.
- These variants led to decreased neural progenitor proliferation.
- The S704C variant impaired neuronal migration in the developing neocortex.
- R264Q and L607F variants failed to rescue DISC1 knockdown-induced aberrant brain development in zebrafish.
Conclusions:
- DISC1 variants impair Wnt signaling and disrupt critical aspects of brain development, including progenitor proliferation and neuron migration.
- These findings provide a mechanistic link between DISC1 variants and neuropsychiatric phenotypes.
More Related Videos
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:41Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...