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OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling

Nature Neuroscience volume 13, pages 690–699 (2010)Cite this article

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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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Figure 1: Pax6 and Tbr2 expression in developing human (a–k) and ferret (l–s) neocortex.
Figure 2: Human OSVZ progenitors express markers of radial glia.
Figure 3: Human and ferret OSVZ progenitors retain basal processes through M phase.
Figure 4: Human OSVZ progenitors have perinuclear centrosomes.
Figure 5: Human and ferret SVZ progenitors have near-random cleavage plane orientation, resulting in asymmetric inheritance of the basal process.
Figure 6: Inhibition of integrin function decreases the population of cycling Pax6-positive, Tbr2-negative SVZ progenitors, but not of cycling Pax6-negative or Tbr2-positive SVZ progenitors, in the E40 ferret neocortex.
Figure 7: Localization of β3-integrin on basal processes of ferret SVZ and ventricular zone progenitors.

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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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Authors and Affiliations

  1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    Simone A Fietz, Iva Kelava, Michaela Wilsch-Bräuninger, Denise Stenzel, Jennifer L Fish & Wieland B Huttner

  2. Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité, Berlin, Germany

    Johannes Vogt & Robert Nitsch

  3. BIOTEC, Technische Universität Dresden, Dresden, Germany

    Denis Corbeil

  4. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Axel Riehn & Wolfgang Distler

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Contributions

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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Correspondence to Wieland B Huttner.

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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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