Role of Intermediate Progenitor Cells in Cerebral Cortex Development
ABSTRACT 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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- "The embryonic neocortex is characterised by high proliferation from E11 to E16.5, by high double-strand DNA breakage and by sensitivity to undergo 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). "
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"
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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- ") . In addition to the VZ , the embryonic sub ventricular zone ( SVZ ) having cells derived from RG is also considered as a major site for neurogenesis ( Noctor et al . , 2001 , 2004 , 2008 ; Tarabykin et al . , 2001 ; Smart et al . , 2002 ; Nieto et al . , 2004 ; Zimmer et al . , 2004 ; Pontious et al . , 2008 ; Kriegstein and Alvarez - Buylla , 2009 ) . Earlier the SVZ was considered to be a site of gliogenesis only ( Altman and Bayer , 1990 ; Takahashi et al . , 1995 ) . Subsequent imaging studies on the divisions of precursor cells within the SVZ have demonstrated their neurogenic potential ( Miyata et al . , 2004 ; Noctor et al . , 2004 )"
ABSTRACT: Radial glial cells (RGs) originally considered to provide scaffold to the radially migrating neurons constitute a heterogeneous population of the regionally variable precursor cells that generate both neurons as well as glia depending upon the location and the timing of development. Hence specific immunohistochemical markers are required to specify their spatiotemporal location and fate in the neurogenic and gliogenic zones. We hypothesize S100β as a potential and unified marker for both primary and secondary progenitors. To achieve this, cryocut sections from rat brains of varied embryonic and postnatal ages were immunolabeled with a combination of antibodies, i.e., S100β + Nestin, Nestin + GFAP and S100β + GFAP. A large population of the primary and secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed S100β and nestin establishing their progenitor nature. A downregulation of both S100β and nestin noticed by the end of the 1st postnatal week marks their differentiation towards neuronal or glial lineage. In view of the absence of co-expression of GFAP (glial fibrillary acidic protein) either with S100β or nestin, the suitability of accepting GFAP as an early marker of RG's was eliminated. Thus the dynamic expression of S100β in both the neural stem cells (NSCs) and RGs during embryonic and early neonatal life is associated with its proliferative potential and migration of undifferentiated neuroblasts and astrocytes. Once they lose their potential for proliferation, the S100β expression is repressed with its reemergence in mature astrocytes. This study provides the first clear evidence of S100β expression throughout the period of neurogenesis and early gliogenesis, suggesting its suitability as a radial progenitor cell marker.Frontiers in Cellular Neuroscience 04/2015; 9. DOI:10.3389/fncel.2015.00087 · 4.29 Impact Factor