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First published online June 28, 2004
doi: 10.1242/10.1242/dev.01202

Development 131, 3423-3432 (2004)
Published by The Company of Biologists 2004
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Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C

Emmanuel Garcion1,*, Aida Halilagic1, Andreas Faissner2 and Charles ffrench-Constant1,{dagger}

1 Cambridge Centre for Brain Repair, and Departments of Medical Genetics and Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
2 Department of Molecular Neurobiology, Ruhr University, Building NDEF 05/593, Universitaetsstraße 150, D44801 Bochum, Germany

{dagger} Author for correspondence (e-mail: cfc{at}mole.bio.cam.ac.uk)

Accepted 24 March 2004

Stem cells in the embryonic mammalian CNS are initially responsive to fibroblast growth factor 2 (FGF2). They then undergo a developmental programme in which they acquire epidermal growth factor (EGF) responsiveness, switch from the production of neuronal to glial precursors and become localized in specialized germinal zones such as the subventricular zone (SVZ). Here we show that extracellular matrix molecules act as regulators of this programme. Tenascin C is highly expressed in the SVZ, and transgenic mice lacking tenascin C show delayed acquisition of the EGF receptor. This results from alterations in the response of the stem cells to the growth factors FGF2 and bone morphogenic protein 4 (BMP4), which normally promote and inhibit acquisition of the EGF receptor, respectively. Tenascin C-deficient mice also have altered numbers of CNS stem cells and these stem cells have an increased probability of generating neurones when grown in cell culture. We conclude that tenascin C contributes to the generation of a stem cell `niche' within the SVZ, acting to orchestrate growth factor signalling so as to accelerate neural stem cell development.

Key words: Tenascin C, Growth factor, Proliferation, Differentiation, Neurogenesis, Gliogenesis, Stem cell, Central nervous system, Neurosphere




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