Role of Intermediate Progenitor Cells in Cerebral Cortex Development

Department of Pathology, University of Washington, Seattle, WA, USA.
Developmental Neuroscience (Impact Factor: 2.7). 02/2008; 30(1-3):24-32. DOI: 10.1159/000109848
Source: PubMed


Intermediate progenitor cells (IPCs) are a type of neurogenic transient amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at basal (abventricular) positions in the neuroepithelium to produce pairs of new neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit progenitors (neuroepithelial cells and radial glia) divide at the apical (ventricular) surface and produce only single neurons or single IPCs by asymmetric division, or self-amplify by symmetric division. Histologically, IPCs are most prominent during the middle and late stages of neurogenesis, when they accumulate in the subventricular zone, a progenitor compartment linked to the genesis of upper neocortical layers (II-IV). Nevertheless, IPCs are present throughout cortical neurogenesis and produce neurons for all layers. In mice, changes in the abundance of IPCs caused by mutations of Pax6, Ngn2, Id4 and other genes are associated with parallel changes in cortical thickness but not surface area. In gyrencephalic brains, IPCs may play broader roles in determining not only laminar thickness, but also cortical surface area and gyral patterns. We propose that regulation of IPC genesis and amplification across developmental stages and regional subdivisions modulates laminar neurogenesis and contributes to the cytoarchitectonic differentiation of cortical areas.

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    • "Pioneering studies describing the structure of the embryonic neocortex have shown that the ventricular zone (VZ) and sub-ventricular zone (SVZ), hereafter VZ/SVZ, adjacent to the ventricles, contain the neural stem and intermediate progenitor cells, which replicate rapidly from E11 to E16.5 (Bayer et al., 1991). The intermediate zone (IZ), which lies above the VZ/SVZ, contains migrating cells and axons (Mitsuhashi and Takahashi, 2009; Pontious et al., 2008). At ∼E14, post-mitotic neurons establish a layer known as the cortical plate (CP) between the IZ and the superficial marginal zone (Fig. 1A). "

    Development 10/2015; 142(20):e1.2-e1.2. DOI:10.1242/dev.131607 · 6.46 Impact Factor
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    • "Sensitive activation of apoptosis in the adult neural stem cells The embryonic neocortex is characterised by high proliferation from E11 to E16.5, high DSB damage and by sensitivity to DSB-induced apoptosis (Bayer et al., 1991; Gatz et al., 2011; Pontious et al., 2008; Saha et al., 2014). Here, we find that cells in the adult SVZ do not incur high levels of DSBs but sensitively activate apoptosis (Fig. 7). "
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    ABSTRACT: The embryonic neural stem cell compartment is characterised by rapid proliferation from E11 to E16.5, high endogenous DNA double-strand break (DSB) formation and marked sensitivity to undergo apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We demonstrate that, although DSBs do not arise at high frequency in adult neural stem cells, DSBs that persist endogenously in Lig4(Y288C) mice or induced by low radiation doses can sensitively activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild type newborn mice. © 2015. Published by The Company of Biologists Ltd.
    Journal of Cell Science 08/2015; DOI:10.1242/jcs.171223 · 5.43 Impact Factor
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    • "vision is associated with vertical cleavage planes , while asymmetric cell divisions is associated with horizontal cleavage planes ( Haydar et al . , 2003 ) . During asymmetric division , one daughter cell remains in the ventricular zone as a radial glial cell , the other one becomes either a postmitotic neuron or an intermediate progenitor cell ( Pontious et al . , 2008 ) . Intermediate progenitor cells eventually undergo terminal symmetric division to create pairs of postmitotic neurons ( Noctor et al . , 2004 ) . As Figure 1 suggests , we can classify radial glial cells and intermediate progenitor cells into two subpopulations , apical and basal : apical radial glial cells and apical intermediate pro"
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    ABSTRACT: Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.
    Frontiers in Cellular Neuroscience 07/2015; 9:257. DOI:10.3389/fncel.2015.00257 · 4.29 Impact Factor
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