| Autor: |
Mori, Nobuko, Kuwamura, Mitsuru, Tanaka, Natsuki, Hirano, Ryuji, Nabe, Mikoto, Ibuki, Masato, Yamate, Jyoji |
| Zdroj: |
American Journal of Pathology; January 2012, Vol. 180 Issue: 1 p314-327, 14p |
| Abstrakt: |
Cortical heterotopia, a malformation of the developing cortex, are a major cause of epilepsy and mental retardation in humans. Hemorrhagic hydrocephalus (hhy) mutation on mouse chromosome 12 results in subcortical heterotopia and nonobstructive hydrocephalus with frequent brain hemorrhage. Here, we show that coiled-coil domain-containing 85C (Ccdc85c), consisting of 6 exons that encode a 420 amino acid protein, is disrupted by replacement of a 3.2-kb sequence, including exon 2 in Ccdc85cby a 1.5-kb retrotransposon-like repeat sequence in the hhymutant. Immunoreactivity to Ccdc85C was detected predominantly at the apical junctions of radial glia in the wall of lateral ventricles of the developing brain. In the hhybrain at embryonic (E) day 18 (E18), radial glial demise followed by agenesis of the ependymal layer lining the neonatal cortex and accumulation of neuronal specific nuclear protein (NeuN)-positive postmigratory neurons in the subcortical area occurred. Accumulation of E15-born, but not of E13-born, 5-bromo-2′-deoxyuridine labeled neurons expressing special AT-rich sequence binding protein 2 was detected in both heterotopia and the superficial layers of the hhyneocortex at postnatal day 7. Ccdc85cdeficiency permitted radial scattering of paired box gene 6-positive neural progenitors in the ventricular zone, likely resulting in reduced self-renewal of the progenitors in the developing hhycortex. These findings indicate an important role of Ccdc85C in cortical development and provide a mouse model to study pathogenesis of subcortical heterotopia and hydrocephalus. |
| Databáze: |
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