Integrins mediate a neuronal survival signal for oligodendrocytes

被引:81
作者
Frost, EE
Buttery, PC
Milner, R
ffrench-Constant, C [1 ]
机构
[1] Univ Forvie Site, Addenbrookes Hosp, Cambridge Ctr Brain Repair, Cambridge CB2 2QQ, England
[2] Wellcome CRC Inst Dev Biol & Canc, Cambridge CB1 1QR, England
[3] Univ Cambridge, Dept Med Genet, Cambridge, England
[4] Addenbrookes Hosp, Dept Neurol, Cambridge CB2 2QQ, England
关键词
D O I
10.1016/S0960-9822(99)80506-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha 6 beta 1 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. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1251 / 1254
页数:4
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