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First published online June 28, 2004
doi: 10.1242/10.1242/dev.01199
1 Departments of Medical Genetics and Pathology, University of Cambridge, Tennis
Court Road, Cambridge CB2 1QP, UK
2 Institute of Cell Biology, Department of Biology, Swiss Federal Institute of
Technology, ETH Hönggerberg, CH-8093 Zürich, Switzerland
3 Department of Molecular Medicine, Max-Planck-Institut für Biochemie, Am
Klopferspitz 18a, D-82152 Martinsried, Germany
* Author for correspondence (e-mail: cfc{at}mole.bio.cam.ac.uk)
Accepted 31 March 2004
The emerging evidence that stem cells develop in specialised niches
highlights the potential role of environmental factors in their regulation.
Here we examine the role of ß1 integrin/extracellular matrix interactions
in neural stem cells. We find high levels of ß1 integrin expression in
the stem-cell containing regions of the embryonic CNS, with associated
expression of the laminin 
2 chain. Expression levels of laminin
2 are reduced in the postnatal CNS, but a population of cells
expressing high levels of ß1 remains. Using neurospheres –
aggregate cultures, derived from single stem cells, that have a
three-dimensional architecture that results in the localisation of the stem
cell population around the edge of the sphere – we show directly that
ß1 integrins are expressed at high levels on neural stem cells and can be
used for their selection. MAPK, but not PI3K, signalling is required for
neural stem cell maintenance, as assessed by neurosphere formation, and
inhibition or genetic ablation of ß1 integrin using cre/lox technology
reduces the level of MAPK activity. We conclude that integrins are therefore
an important part of the signalling mechanisms that control neural stem cell
behaviour in specific areas of the CNS.
Key words: Extracellular matrix, Laminin, Fibronectin, Neurosphere, Cre/lox, Stem cell niche, Ventricular zone, Subventricular zone
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