Abstract
A major cause of the cerebral cortex expansion that occurred during evolution is the increase in subventricular zone (SVZ) progenitors. We found that progenitors in the outer SVZ (OSVZ) of developing human neocortex retain features of radial glia, in contrast to rodent SVZ progenitors, which have limited proliferation potential. Although delaminating from apical adherens junctions, OSVZ progenitors maintained a basal process contacting the basal lamina, a canonical epithelial property. OSVZ progenitor divisions resulted in asymmetric inheritance of their basal process. Notably, OSVZ progenitors are also found in the ferret, a gyrencephalic nonprimate. Functional disruption of integrins, expressed on the basal process of ferret OSVZ progenitors, markedly decreased the OSVZ progenitor population size, but not that of other, process-lacking SVZ progenitors, in slice cultures of ferret neocortex. Our findings suggest that maintenance of this epithelial property allows integrin-mediated, repeated asymmetric divisions of OSVZ progenitors, providing a basis for neocortical expansion.
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Acknowledgements
We thank J. Helppi and other members of the animal facility, and the light microscopy facility, of the Max Planck Institute of Molecular Cell Biology and Genetics for excellent support, A.-M. Marzesco and E. Taverna for experimental advice, C. Haffner for excellent technical assistance, S. Preibisch for developing the Fiji plug-in, and J. Pulvers for his helpful comments on the manuscript. We are grateful to the Bundesinstitut für Risikobewertung and Biotie Therapies for ferret housing. S.A.F., I.K. and J.L.F. were members of the International Max Planck Research School for Molecular Cell Biology and Bioengineering. W.B.H. was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) (SFB 655, A2) and by the DFG-funded Center for Regenerative Therapies Dresden and by the Fonds der Chemischen Industrie.
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S.A.F. performed the experiments on human tissue. S.A.F. and I.K. contributed equally to the experiments on ferret tissue and co-wrote the paper. J.V. provided human tissue and gave advice on the experiments. M.W.-B. performed the electron microscopy analyses. D.S. proposed the use of echistatin and contributed to some experiments. D.C. provided reagents for prominin-1 analyses. J.L.F., A.R., W.D. and R.N. provided human tissue. W.B.H. supervised the project and wrote the paper.
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Fietz, S., Kelava, I., Vogt, J. et al. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat Neurosci 13, 690–699 (2010). https://doi.org/10.1038/nn.2553
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DOI: https://doi.org/10.1038/nn.2553
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