Increased neuronal production, enlarged forebrains and cytoarchitectural distortions in beta-catenin overexpressing transgenic mice.
beta-Catenin can function in the decision of neural precursors to proliferate or differentiate during mammalian neuronal development and may regulate cerebral cortical size by controlling the generation of neural precursor cells. Mice expressing high levels of a stabilized beta-catenin transgene in neural precursors develop enlarged brains with expanded precursor populations, increased cerebral cortical surface area, and folds resembling sulci and gyri of higher mammals present at birth. Here we report the effects in adult mice expressing lower levels of the same stabilized beta-catenin transgene in neural precursors. Adult transgenic animals develop enlarged forebrains with thin cerebral cortices with increased surface area, expanded subventricular zones with subcortical aggregations of neurons and enlarged, distorted hippocampi. The brains from transgenic mice also show apparent arrest of neuronal migration and dramatic disorganization of the layering of the cerebral cortex. These findings suggest that beta-catenin can cause expansion of the precursor pool resulting in increased neuronal production and greater brain size and suggest a crucial role for beta-catenin in neuronal migration and cortical lamination.
Chenn
Anjen
A
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611-3008, USA. achenn@northwestern.edu
Walsh
Christopher A
CA
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002465:Cell Movement; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology* / Q000502:physiology; D002552:Cerebral Ventricles / Q000002:abnormalities*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D016548:Prosencephalon / Q000002:abnormalities*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin