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Wrong place, wrong time: ectopic progenitors cause cortical heterotopias

Nature Neuroscience volume 17, pages 894–895 (2014)Cite this article

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A report reveals that giant subcortical heterotopia is caused by mutation of a microtubule-associated protein, Eml1. Defects in Eml1 lead to disruption of the radial migratory scaffolding network in mice and humans.

In this issue of Nature Neuroscience, Kielar et al.11 elegantly examine an extensive cortical malformation syndrome that they show is caused by mutations in mice and humans that result in the formation of massive subcortical heterotopias not because of primary defects in neuronal migration competence, but rather as a result of abnormalities in the plane of cell division, detachment of mitotic cells from the VZ and defects in the radial migratory scaffolding. The authors found that the HeCo mouse model of heterotopia12 shows cortical developmental defects that are marked by the presence of ectopic progenitors outside the ventricular zone, as well as defects in the radial glial cell scaffolding, progenitor proliferation and cortical organization. Furthermore, the mouse histology recapitulates human magnetic resonance imaging phenotypes in patients with mutations in the corresponding gene and a rare syndrome called giant subcortical heterotopia13.

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Figure 1: Schematic diagram showing aspects of normal cortical development and the point at which development is disrupted in HeCo mice.

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Authors and Affiliations

  1. Laura Cocas and Samuel J. Pleasure are in the Department of Neurology San Francisco, California, USA.,

    Laura Cocas & Samuel J Pleasure

  2. Samuel J. Pleasure is in the Program in Neuroscience, Program in Developmental and Stem Cell Biology, and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, USA.,

    Samuel J Pleasure

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  1. Laura Cocas
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  2. Samuel J Pleasure
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Correspondence to Samuel J Pleasure.

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Cocas, L., Pleasure, S. Wrong place, wrong time: ectopic progenitors cause cortical heterotopias. Nat Neurosci 17, 894–895 (2014). https://doi.org/10.1038/nn.3747

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