CNS integrins switch growth factor signalling to promote target-dependent survival

Holly Colognato, Wia Baron, Virginia Avellana-Adalid, Jõao B. Relvas, Anne Baron-Van Evercooren, Elisabeth Georges-Labouesse, Charles French-Constant

Research output: Contribution to journalArticlepeer-review

202 Citations (Scopus)

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 α6 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.

Original languageEnglish
Pages (from-to)833-841
Number of pages9
JournalNature Cell Biology
Volume4
Issue number11
DOIs
Publication statusPublished - 14 Oct 2002

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