Does Cell Lineage in the Developing Cerebral Cortex Contribute to its Columnar Organization?

Edmond and Lily Safra International Institute of Neuroscience of Natal, Natal, Rio Grande do Norte Brazil.
Frontiers in Neuroanatomy (Impact Factor: 3.54). 06/2010; 4:26. DOI: 10.3389/fnana.2010.00026
Source: PubMed


Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone (VZ) could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighboring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell-cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits.

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Available from: Cecilia Hedin-Pereira, Sep 30, 2015
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    • "Such functional columns are often termed " barrels " or " intracortical modules " by neurophysiologists, and the pattern of dendritic bundles and of thalamocortical projections may determine their integrity (Feldmeyer et al., 2013; Li et al., 2013; Rockland and Ichinohe, 2004). Nevertheless, some investigators remain reserved or skeptical of the importance of functional columns in the mature brain (da Costa and Martin, 2010; Horton and Adams, 2005). In FCD1a, some areas of dysplastic cortex show no architectural organization, the neurons seemingly disoriented and displaced without recognizable vertical or horizontal lamination. "
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    ABSTRACT: Cerebral malformations are best understood as abnormal tissue morphogenesis in the context of disorders of ontogenesis. In neuroembryology, the timing of onset and duration of abnormal genetic expression and neurodevelopmental processes are primordial and must always be assessed, regardless whether the dysgenesis is primarily genetic in origin or acquired in utero due to ischemia, fetal infarcts that interrupt cellular migration or exposure to teratogenic drugs or neurotoxins. Defective timing interferes with the synchrony between different developmental processes, such as synaptogenesis in relation to other aspects of neuronal maturation. Timing may be delay or arrest development at an immature stage or may be precocious but asynchronous with other developmental features. Focal cortical dysplasia (FCD) types 1 and 3 may be arrested maturation of the radial microcolumnar neocortical architecture that is normal in the first half of gestation, without the expected transition to a horizontal or tangential laminar cortical architecture in the second half. Lack of lamination in either the vertical or horizontal planes may be due to defective extracellular adhesion molecules that cause detachment of migratory neuroblasts from their radial glial guide fibers, to enable recently arriving neuroblasts to bypass those already in place within the cortical plate for the programmed inside-out neuronal arrangement. FCD type 2 has a different pathogenesis. The megalocytic and dysmorphic neurons may result from somatic mutations of some, but not all, neuronal precursors in the periventricular region. FCD2 and hemimegalencephaly (HME) may have the same pathogenesis, the principal difference being timing of onset within the 33 mitotic cycles of the periventricular neuroepithelium to exponentially produce the total neuronal population of the cerebral cortex: if the mutation occurs during the late mitotic cycles, FCD2 results as a small dysgenesis; if the mutation occurs in the early mitotic cycles, the distribution of abnormal neurons is more extensive and HME may result. Why some cerebral malformations are more epileptogenic than others, despite similar histological features, remains enigmatic but probably involves differences in synaptic circuitry among individual cases.
    Progress in brain research 09/2014; 213C:181-198. DOI:10.1016/B978-0-444-63326-2.00010-7 · 2.83 Impact Factor
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    • "The mammalian neocortex comprises six layers, each containing neurons with its own morphology, functional properties and connections as well as time of origin. Neocortex formation during development is generated in an inside-out pattern, with the oldest neurons (layer VI) closest and the youngest neurons (layers II/III) farthest from their birthplace near the ventricle [1-4]. The region where migration stops is defined by a layer of specialized pioneer neurons called Cajal-Retzius cells, which migrate tangentially early during development [5]. "
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    ABSTRACT: Background During rat development, histamine (HA) is one of the first neuroactive molecules to appear in the brain, reaching its maximal value at embryonic day 14, a period when neurogenesis of deep layers is occurring in the cerebral cortex, suggesting a role of this amine in neuronal specification. We previously reported, using high-density cerebrocortical neural precursor cultures, that micromolar HA enhanced the effect of fibroblast growth factor (FGF)-2 on proliferation, and that HA increased neuronal differentiation, due to HA type 1 receptor (H1R) activation. Results Clonal experiments performed here showed that HA decreased colony size and caused a significant increase in the percentage of clones containing mature neurons through H1R stimulation. In proliferating precursors, we studied whether HA activates G protein-coupled receptors linked to intracellular calcium increases. Neural cells presented an increase in cytoplasmic calcium even in the absence of extracellular calcium, a response mediated by H1R. Since FGF receptors (FGFRs) are known to be key players in cell proliferation and differentiation, we determined whether HA modifies the expression of FGFRs1-4 by using RT-PCR. An important transcriptional increase in FGFR1 was elicited after H1R activation. We also tested whether HA promotes differentiation specifically to neurons with molecular markers of different cortical layers by immunocytochemistry. HA caused significant increases in cells expressing the deep layer neuronal marker FOXP2; this induction of FOXP2-positive neurons elicited by HA was blocked by the H1R antagonist chlorpheniramine in vitro. Finally, we found a notable decrease in FOXP2+ cortical neurons in vivo, when chlorpheniramine was infused in the cerebral ventricles through intrauterine injection. Conclusion These results show that HA, by activating H1R, has a neurogenic effect in clonal conditions and suggest that intracellular calcium elevation and transcriptional up-regulation of FGFR1 participate in HA-induced neuronal differentiation to FOXP2 cells in vitro; furthermore, H1R blockade in vivo resulted in decreased cortical FOXP2+ neurons.
    Neural Development 03/2013; 8(1):4. DOI:10.1186/1749-8104-8-4 · 3.45 Impact Factor
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    • "Both in vivo and in vitro experiments assure that a single neocortical progenitor generates multiple layer-specific subtypes . For example, in cell lineage tracing, a single progenitor generates clonally-related neurons that are radially distributed across the neocortical layers (Luskin et al. 1988; Price & Thurlow 1988; Walsh & Cepko 1990; Kornack & Rakic 1995; Reid et al. 1997; Noctor et al. 2001; Costa & Hedin-Pereira 2010). Preferential synaptic connections among these clonally related neurons are suggested to be the developmental basis for constructing the radial columnar unit of neural circuits (Yu et al. 2009, 2012; Li et al. 2012; Ohtsuki et al. 2012). "
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    ABSTRACT: The neocortex facilitates mammalian adaptive radiation by conferring highly sophisticated cognitive and motor abilities. A unique feature of the mammalian neocortex is its laminar structure in which similar neuronal subtypes are arranged in tangential layers and construct columnar circuits via interlaminar connections. The neocortical layer structure is completely conserved among all mammalian species, including monotremes and marsupials. However, this structure is missing in non-mammalian sister groups, such as birds and reptiles. The evolutionary origins of neocortical layers and cytoarchitectural borders have been the subject of debate over the past century. Using the chicken embryos as a model of evolutionary developmental biology (evo-devo model), we recently provided evidence suggesting that the evolutionary origin of layer-specific neuron subtypes predates the emergence of laminar structures. Based on this finding, we review the evolutionary conservation and divergence of neocortical development between mammals and non-mammals and discuss how the layered cytoarchitecture of the mammalian neocortex originated during evolution.
    Development Growth and Regeneration 12/2012; DOI:10.1111/dgd.12020 · 2.42 Impact Factor
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