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First published online 31 May 2005
doi: 10.1242/jcs.02396

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Regulation of neural progenitor proliferation and survival by ß1 integrins

Dino P. Leone^1,*,, João B. Relvas^1,*, Lia S. Campos^2,, Silvio Hemmi³, Cord Brakebusch⁴, Reinhard Fässler⁴, Charles ffrench-Constant² and Ueli Suter^1,¶

¹ Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zürich, Switzerland
² Departments of Medical Genetics and Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
³ Institute of Molecular Biology Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland
⁴ Department of Molecular Medicine, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany

^¶ Author for correspondence (e-mail: usuter{at}cell.biol.ethz.ch)

Accepted 22 March 2005

Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that ß1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the ß1-integrin allele, and consequent loss of ß1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates is also impaired. These effects can be partially compensated by the addition of exogenous growth factors. Thus, ß1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.

Key words: Integrins, Neural progenitors, Neurospheres, CNS

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