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JCS ePress online publication date 31 May 2005
doi: 10.1242/jcs.02396

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Research Article

Regulation of neural progenitor proliferation and survival by {beta}1 integrins


Dino P. Leone, João B. Relvas, Lia S. Campos, Silvio Hemmi, Cord Brakebusch, Reinhard Fässler, Charles ffrench-Constant, and Ueli Suter*
* Author for correspondence (e-mail: usuter{at}cell.biol.ethz.ch)

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 {beta}1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the {beta}1-integrin allele, and consequent loss of {beta}1-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, {beta}1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.


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