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Colognato/Macmillan# R4 l- I9 p+ }: F7 n4 |

$ |9 w1 _; [: T0 a8 V- C+ ZAsingle factor can promote both p
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/ b3 A3 G' \8 ]) [8 kroliferation and differentiation of oligodendrocytes, according to Holly Colognato, Charles ffrench-Constant (University of Cambridge, Cambridge, UK), and colleagues. The added ingredient that makes the difference, and switches the signaling pathway downstream of the growth factor, is the extracellular protein laminin.1 }$ N5 g/ c8 d

# U7 v4 |/ c8 b. uThe laminin is found on axons in the central nervous system—the target of the oligodendrocytes. Before arriving at this target, the oligodendrocytes proliferate under the influence of several factors including neuregulin, whose actions are pro-proliferation and anti-differentiation.
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As the cells mature, a proapoptotic protein called BAD accumulates. This may result in the death of excess oligodendrocytes that are far away from their target. But the Cambridge group found that cells close enough to an axon could counteract the accumulation of BAD. The ligation of oligodendrocyte integrin 6 with axon-supplied laminin causes a switch in signaling downstream of neuregulin. The PI3K proliferation signal is replaced with a MAP kinase differentiation signal that also phosphorylates and thus inactivates BAD.
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% `! \- W) d1 d0 e( L  Y$ xColognato does not yet know whether integrin interferes at the level of the plasma membrane or further down the signaling cascade. But she is intrigued to see whether developmental regulation of the pathways might explain a mystery of repair: that newly arriving oligodendrocytes often fail to myelinate adult axons in diseases such as multiple sclerosis.
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- M0 C8 d  C) A& ?& j- uColognato, H., et al. 2002. Nat. Cell Biol. 10.1038/ncb865.(Oligodendrocytes (green) get modified by)