Integrins mediate a neuronal survival signal for oligodendrocytes

Frost, Emma E., Buttery, Philip C., Milner, Richard and Ffrench-Constant, Charles ORCID: (1999) Integrins mediate a neuronal survival signal for oligodendrocytes. Current Biology, 9 (21). pp. 1251-1254. ISSN 0960-9822

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Target-dependent survival of newly differentiated cells is an important part of neural development. In the case of myelin-forming oligodendrocytes, it matches the number of oligodendrocytes to the available axons [1]. in addition to growth factors, an axonal signal regulates this survival: when axons are transected, oligodendrocytes die and, conversely, when the number of axons is increased by genetic manipulation, oligodendrocyte numbers increase [2,3]. Newly formed oligodendrocytes that fail to contact axons undergo apoptosis, and co-culture experiments that model axon-glial interactions in vitro reveal a neuronal survival effect not present in neuron-conditioned medium [4,5], suggesting that the signal is non-diffusible and present on the surface of axons. The nature of these neuronal signals is unknown, as are the mechanisms by which they interact with growth-factor-mediated survival signals. As integrins can regulate survival in other cell types [6-8], we determined whether integrins are involved in the neuronal survival effect. We found that the laminin receptor α6β1 integrin, which is expressed on oligodendrocytes, enhances the sensitivity of oligodendrocytes to the survival effect of growth factors. On the basis of this interaction between integrin and growth-factor-mediated signalling, we propose a simple model by which signals from axons and other cell types might interact to regulate oligodendrocyte cell numbers.

Item Type: Article
Additional Information: Funding Information: We thank J. Cohen (Guy's Hospital) for advice on the DRG cultures and C. Streuli (Manchester University), M. Horton (UCL) and S. Goodman (Merck) for essential reagents. This work was funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Wellcome Trust and by a MRC clinical training fellowship to P.C.B.
Uncontrolled Keywords: neuroscience(all),biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 13:30
Last Modified: 22 Oct 2022 18:38
DOI: 10.1016/s0960-9822(99)80506-5

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