Abstract
Embryonic germinal zones of the dorsal and ventral telencephalon generate cortical neurons during the final week of gestation in rodent and during several months in human. Whereas the vast majority of cortical interneurons originate from the ventral telencephalon, excitatory neurons are locally generated within the germinal zone of the dorsal telencephalon, the future cerebral cortex, itself. However, a number of studies have described proliferating cells external to the ventricular and subventricular germinal zones in the developing dorsal telencephalon. In this study, we performed a comprehensive cell density analysis of such ‘extra-ventricular proliferating cells’ (EVPCs) during corticogenesis in rat and human using a mitotic marker anti-phospho-histone H3. Subsequently, we performed double-labelling studies with other mitotic and cell type specific markers to undertake phenotypic characterisation of EVPCs. Our findings show: (1) the densities of extra-ventricular H3-positive (H3+) cells were surprisingly similar in preplate stage rat and human; (2) extra-ventricular proliferation continues during mid-and late corticogenesis in rat and in early fetal human cortex; and (3) extra-ventricular cells appear to be mitotic precursors as they are not immunoreactive for a panel of early post-mitotic and cell type-specific markers, although (4) a subset of EVPCs are proliferating microglia. These data suggest that some aspects of early corticogenesis are conserved between rodent and human despite marked differences in the duration of neurogenesis and the anatomical organisation of the developing cerebral cortex.
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Acknowledgments
This work was supported by Grants from The European Community (QLRT-1999-30158), The Wellcome Trust (063974/B/01/Z), Human Frontier Science Program (RGP0107/2001), Medical Research Council and RGBI 01-04-48819. RSEC was supported by a MRC studentship and Mary Goodger Scholarship (Oxford Medical Science Division). We are grateful to Dr. Henry Kennedy, Dr. Colette Dehay, Dr. Wieland Huttner, Dr. Alessio Attardo and Dr. Joshua Corbin for their thoughtful comments on a previous version of this manuscript and Prof. Colin Blakemore for valuable discussions regarding this study. The authors would also like to thank Drs. Huttner and Attardo for providing the Tis21-GFP brains used in this study. Dr. Ole Paulsen kindly provided advice on quantitative analysis.
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Carney, R.S.E., Bystron, I., López-Bendito, G. et al. Comparative analysis of extra-ventricular mitoses at early stages of cortical development in rat and human. Brain Struct Funct 212, 37–54 (2007). https://doi.org/10.1007/s00429-007-0142-4
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DOI: https://doi.org/10.1007/s00429-007-0142-4