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

• Type: Article in International Scientific Journal
• Date: 2002

Authors

Colognato, H (Author) Other; Baron, W (Author) Other; Avellana Adalid, V (Author) Other; Relvas, JB (Author) Other; Baron Van Evercooren, A (Author) Other; Georges Labouesse, E (Author) Other; ffrench Constant, C (Author) Other

Journal

Title: Nature Cell Biology

Vol. 4

Pages: 833-841

ISSN: 1465-7392

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 175 Citations

Scopus - 198 Citations

Other information

Authenticus ID: P-00F-Q00

DOI: 10.1038/ncb865

Abstract (EN): 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 alpha(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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9