Chenn, A. & Walsh, C.A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365-369

Brigham and Women's Hospital, Boston, Massachusetts, United States
Science (Impact Factor: 31.48). 08/2002; 297(5580):365-9. DOI: 10.1126/science.1074192
Source: PubMed

ABSTRACT Transgenic mice expressing a stabilized beta-catenin in neural precursors develop enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Brains from transgenic animals have enlarged lateral ventricles lined with neuroepithelial precursor cells, reflecting an expansion of the precursor population. Compared with wild-type precursors, a greater proportion of transgenic precursors reenter the cell cycle after mitosis. These results show that beta-catenin can function in the decision of precursors to proliferate or differentiate during mammalian neuronal development and suggest that beta-catenin can regulate cerebral cortical size by controlling the generation of neural precursor cells.

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Available from: Anjen Chenn, Aug 29, 2015
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    • "This view of gyrification as the aggregate of multiple factors which contribute to surface expansion fits with observations of how genes and transcription factors (TFs) variously induce morphological abnormalities. These have been extensively reviewed elsewhere (Hevner 2006), but point to the general principle that those factors which promote surface expansion through an increase in progenitor proliferation (in particular proliferation of radial glia) result in an increase in surface expansion and hence gyrification (Chenn and Walsh 2002). For example, FGF2, the manipulation of which can be used to induce folding, promotes RG self-renewal leading to an increase in tangential cortical expansion (Rash et al. 2013). "
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    ABSTRACT: Cortical gyrification is not a random process. Instead, the folds that develop are synonymous with the functional organization of the cortex, and form patterns that are remarkably consistent across individuals and even some species. How this happens is not well understood. Although many developmental features and evolutionary adaptations have been proposed as the primary cause of gyrencephaly, it is not evident that gyrification is reducible in this way. In recent years, we have greatly increased our understanding of the multiple factors that influence cortical folding, from the action of genes in health and disease to evolutionary adaptations that characterize distinctions between gyrencephalic and lissencephalic cortices. Nonetheless it is unclear how these factors which influence events at a small-scale synthesize to form the consistent and biologically meaningful large-scale features of sulci and gyri. In this article, we review the empirical evidence which suggests that gyrification is the product of a generalized mechanism, namely the differential expansion of the cortex. By considering the implications of this model, we demonstrate that it is possible to link the fundamental biological components of the cortex to its large-scale pattern-specific morphology and functional organization.
    Brain Structure and Function 12/2014; DOI:10.1007/s00429-014-0961-z · 4.57 Impact Factor
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    • "Importantly , in vivo expression of GSK - 3 cannot be inhibited by serine - phosphorylation – impaired neurogenesis in mice and blocked the enhancement of neuro - genesis induced by co - administration of lithium and fluoxetine ( Eom and Jope , 2009 ) . Moreover , in adult transgenic mice that express the stabilized form of β - catenin , which lacks the GSK - 3β phosphorylation site , the SVZ is enlarged ( Chenn and Walsh , 2002 ) . Retroviral - mediated expression of a stabilized β - catenin protein or administration of a specific inhibitor of GSK - 3β pro - moted the proliferation of progenitor cells in the adult mouse brain ( Adachi et al . "
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    ABSTRACT: It is generally accepted that chronic treatment with antidepressants increases hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signalling was shown to be involved in the mechanism of how antidepressants might influence hippocampal neurogenesis. The aim of this study was to determine whether GSK-3β/β-catenin signalling is involved in the alteration of neurogenesis as a result of treatment with fluoxetine, a selective serotonin reuptake inhibitor. The mechanisms involved in fluoxetine's regulation of GSK-3β/β-catenin signalling pathway were also examined. Our results demonstrated that fluoxetine increased the proliferation of embryonic neural precursor cells (NPCs) by upregulating the phosphorylation of Ser9 on GSK-3β and increasing the level of nuclear β-catenin. The overexpression of a stabilised β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine. The effects of fluoxetine-induced upregulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635. The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signalling pathway that links postsynaptic 5-HT1A receptor activation. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 12/2014; 18(5). DOI:10.1093/ijnp/pyu099 · 5.26 Impact Factor
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    • "Since CV is the function of CT and SA, only assessing CV may obscure individual differences. More importantly , SA and CT carry distinct characteristics which are driven by different genetic (Eyler et al., 2012; Panizzon et al., 2009; Winkler et al., 2010) and cellular processes (Chenn and Walsh, 2002). While SA is thought to reflect the number and spacing of cortical columns, CT relates to the neuronal density (Casanova and Tillquist, 2008; La Fougère et al., 2011; Rakic, 2009). "
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    ABSTRACT: Background Trait impulsivity is commonly associated with cocaine dependence. The few studies that have investigated the relation between trait impulsivity and cortical morphometry, have shown a distinct relation between impulsivity and cortical volume (CV) of temporal, frontal and insula cortex. As CV is the function of cortical surface area (SA) and cortical thickness (CT) impulsivity may be differently associated to SA than to CT. Method Fifty-three cocaine users (CU) and thirty-five controls (HC) (males aged 18-55 years) completed the Barrat Impulsiveness Scale and a structural scan was made on a 3T MRI scanner. CV, SA and CT were measured using Freesurfer. Multivariate analysis was used to test for group differences and group by impulsivity interaction effects in CV, SA and ST across 9 regions of interest in the temporal, frontal and insular cortices. Possible confounding effects of drug- and alcohol exposure were explored. Results Compared to HC, CU had a smaller SA of the superior temporal cortex but a larger SA of the insula. There were divergent relations between trait impulsivity and SA of the superior temporal cortex and insula (positive in HC, negative in CU) and CT of the anterior cingulate cortex (negative in HC, positive in CU). Within CU, there was a negative association between monthly cocaine use and CT of the insula and superior temporal cortex. Discussion The distinct relation between trait impulsivity and cortical morphometry in CU and HC might underlie inefficient control over behavior resulting in maladaptive impulsive behaviour such as cocaine abuse.
    Drug and Alcohol Dependence 09/2014; 144. DOI:10.1016/j.drugalcdep.2014.09.016 · 3.28 Impact Factor
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