Article abstract
Nature Cell Biology 4, 833 - 841 (2002)
Published online: 14 October 2002 | doi:10.1038/ncb865
CNS integrins switch growth factor signalling to promote target-dependent survival
Holly Colognato1, Wia Baron1, Virginia Avellana-Adalid2, Jõao B. Relvas1, Anne Baron-Van Evercooren2, Elisabeth Georges-Labouesse3 & Charles ffrench-Constant1
Abstract
Depending on the stage of development, a growth factor can mediate cell proliferation, survival or differentiation. The interaction of cell-surface integrins with extracellular matrix ligands can regulate growth factor responses and thus may influence the effect mediated by the growth factor. Here we show, by using mice lacking the 
6 integrin receptor for laminins, that myelin-forming oligodendrocytes activate an integrin-regulated switch in survival signalling when they contact axonal laminins. This switch alters survival signalling mediated by neuregulin from dependence on the phosphatidylinositol-3-OH kinase (PI(3)K) pathway to dependence on the mitogen-activated kinase pathway. The consequent enhanced survival provides a mechanism for target-dependent selection during development of the central nervous system. This integrin-regulated switch reverses the capacity of neuregulin to inhibit the differentiation of precursors, thereby explaining how neuregulin subsequently promotes differentiation and survival in myelinating oligodendrocytes. Our results provide a general mechanism by which growth factors can exert apparently contradictory effects at different stages of development in individual cell lineages.
- Departments of Medical Genetics and Pathology, and Center for Brain Repair, University of Cambridge, Cambridge CB2 2PY, UK
- Laboratoire des Pathologies de la Myeline, INSERM, CJF 97-11, 75634 Paris Cedex 13, France
- Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch, C.U. de Strasbourg, France
Correspondence to: Charles ffrench-Constant1 e-mail: cfc@mole.bio.cam.ac.uk
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3 integrins
