Prenatal β-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors
| Autor: | Belinson, H, Nakatani, J, Babineau, BA, Birnbaum, RY, Ellegood, J, Bershteyn, M, McEvilly, RJ, Long, JM, Willert, K, Klein, OD, Ahituv, N, Lerch, JP, Rosenfeld, MG, Wynshaw-Boris, A |
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| Rok vydání: | 2016 |
| Předmět: |
Intellectual and Developmental Disabilities (IDD)
Dishevelled Proteins Stereotypic Movement Disorder Nerve Tissue Proteins Medical and Health Sciences Mice Neural Stem Cells Behavioral and Social Science Genetics Animals Humans 2.1 Biological and endogenous factors Aetiology Wnt Signaling Pathway beta Catenin Neurons Pediatric Psychiatry Behavior Animal Psychology and Cognitive Sciences Signal Transducing Neurosciences Brain Adaptor Proteins Biological Sciences Phosphoproteins Stem Cell Research Brain Disorders Wnt Proteins Mental Health POU Domain Factors Neurological Stem Cell Research - Nonembryonic - Non-Human Stereotyped Behavior T-Box Domain Proteins Signal Transduction |
| Zdroj: | Molecular psychiatry, vol 21, iss 10 |
| Popis: | Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a β-catenin/Brn2/Tbr2 transcriptional cascade. Transient pharmacological activation of the canonical Wnt pathway during this period of early corticogenesis rescued the β-catenin/Brn2/Tbr2 transcriptional cascade and the embryonic brain phenotypes. Remarkably, this embryonic treatment prevented adult behavioral deficits and partially rescued abnormal brain structure in Dvl mutant mice. Our findings define a mechanism that links fetal brain development and adult behavior, demonstrating a fetal origin for social and repetitive behavior deficits seen in disorders such as autism. |
| Databáze: | OpenAIRE |
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