Nature Cell Biology4, 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
1
Departments of Medical Genetics and Pathology, and Center for Brain Repair, University of Cambridge, Cambridge CB2 2PY, UK
2
Laboratoire des Pathologies de la Myeline, INSERM, CJF 97-11, 75634 Paris Cedex 13, France
3
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch, C.U. de Strasbourg, France
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
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.
v
3 integrins
