Decision by division: Making cortical maps

Department of Neurobiology and Kavli Institute of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Trends in Neurosciences (Impact Factor: 13.56). 05/2009; 32(5):291-301. DOI: 10.1016/j.tins.2009.01.007
Source: PubMed


In the past three decades, mounting evidence has revealed that specification of the basic cortical neuronal classes starts at the time of their final mitotic divisions in the embryonic proliferative zones. This early cell determination continues during the migration of the newborn neurons across the widening cerebral wall, and it is in the cortical plate that they attain their final positions and establish species-specific cytoarchitectonic areas. Here, the development and evolutionary expansion of the neocortex is viewed in the context of the radial unit and protomap hypotheses. A broad spectrum of findings gave insight into the pathogenesis of cortical malformations and the biological bases for the evolution of the modern human neocortex. We examine the history and evidence behind the concept of early specification of neurons and provide the latest compendium of genes and signaling molecules involved in neuronal fate determination and specification.

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Available from: Albert Ayoub, Oct 01, 2015
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    • "Recently, Chen and colleagues investigated older human adult twins and demonstrated that genetic topography exhibited anterior–posterior and dorsal–ventral organizational gradients on a coarse level (Chen et al. 2011). This level of patterning by opposing gradients is supported by animal studies that used experimental inhibition or overexpression of specific genes (Bishop et al. 2000; O'Leary et al. 2007; Rakic et al. 2009). However, evidence of genetic influences on a finer scale has been sparse. "
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    ABSTRACT: Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Cerebral Cortex 08/2015; DOI:10.1093/cercor/bhv176 · 8.67 Impact Factor
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    • "Eph-ephrin interactions regulate a variety of neurodevelopmental processes, including axonal guidance, migration and apoptosis, in addition to proliferation (Drescher et al., 1997; Flanagan and Vanderhaeghen, 1998; Depaepe et al., 2005; Zimmer et al., 2008; North et al., 2009; Rudolph et al., 2010), and are crucial for establishing thalamocortical projections (Donoghue and Rakic, 1999; Šestan et al., 2001; Bolz et al., 2004). Despite intensive discussion as to whether cortical development is mainly regulated by intrinsic and/or extrinsic cues (Rakic, 1988, 1991; Dehay et al., 2001; Rakic et al., 2009; Zhou et al., 2010; Reillo et al., 2011), the thalamic influence on cortical progenitors and neurogenesis remains debated. Here, we provide further evidence for the extra-cortical regulation of cortical progenitors and hence the final output of neurons by thalamic afferents via the Eph/ephrin system. "
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    ABSTRACT: The phenotype of excitatory cerebral cortex neurons is specified at the progenitor level, orchestrated by various intrinsic and extrinsic factors. Here, we provide evidence for a subcortical contribution to cortical progenitor regulation by thalamic axons via ephrin A5-EphA4 interactions. Ephrin A5 is expressed by thalamic axons and represents a high-affinity ligand for EphA4 receptors detected in cortical precursors. Recombinant ephrin A5-Fc protein, as well as ephrin A ligand-expressing, thalamic axons affect the output of cortical progenitor division in vitro. Ephrin A5-deficient mice show an altered division mode of radial glial cells (RGCs) accompanied by increased numbers of intermediate progenitor cells (IPCs) and an elevated neuronal production for the deep cortical layers at E13.5. In turn, at E16.5 the pool of IPCs is diminished, accompanied by reduced rates of generated neurons destined for the upper cortical layers. This correlates with extended infragranular layers at the expense of superficial cortical layers in adult ephrin A5-deficient and EphA4-deficient mice. We suggest that ephrin A5 ligands imported by invading thalamic axons interact with EphA4-expressing RGCs, thereby contributing to the fine-tuning of IPC generation and thus the proper neuronal output for cortical layers. © 2015. Published by The Company of Biologists Ltd.
    Development 12/2014; 142(1). DOI:10.1242/dev.104927 · 6.46 Impact Factor
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    • "Similarly, the highly visual marmoset monkey (Callithrix jacchus) visual cortex comprises more areas and enhanced visual ability but a comparatively smaller brain than the cat. Therefore, the evolutionary expansion of the neocortical surface (Rakic et al., 2009) does not directly correlate with the addition of visual areas in higher species (Kaas, 1997). It has been proposed that the complexity of neural system, corresponding to the number of cortical divisions and subcortical nuclei, increases with the establishment of a new mammalian order (Manger, 2005). "
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    ABSTRACT: The integration of the visual stimulus takes place at the level of the neocortex, organized in anatomically distinct and functionally unique areas. Primates, including humans, are heavily dependent on vision, with approximately 50% of their neocortical surface dedicated to visual processing and possess many more visual areas than any other mammal, making them the model of choice to study visual cortical arealisation. However, in order to identify the mechanisms responsible for patterning the developing neocortex, specifying area identity as well as elucidate events that have enabled the evolution of the complex primate visual cortex, it is essential to gain access to the cortical maps of alternative species. To this end, species including the mouse have driven the identification of cellular markers, which possess an area-specific expression profile, the development of new tools to label connections and technological advance in imaging techniques enabling monitoring of cortical activity in a behaving animal. In this review we present non-primate species that have contributed to elucidating the evolution and development of the visual cortex. We describe the current understanding of the mechanisms supporting the establishment of areal borders during development, mainly gained in the mouse thanks to the availability of genetically modified lines but also the limitations of the mouse model and the need for alternate species.
    Frontiers in Neural Circuits 07/2014; 8:79. DOI:10.3389/fncir.2014.00079 · 3.60 Impact Factor
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