Charnay Patrick, Coulpier Fanny, Decker Laurence, Funalot Benoît, Vallat Jean-Michel, Garcia-Bragado Federico, Topilko Piotr
INSERM, U1024, CNRS UMR 8197, Ecole Normale Supérieure, Plate-forme Transcriptome, IBENS, 46 rue d'Ulm, 75230 Paris Cédex 05, France.
Bull Acad Natl Med. 2010 Apr-May;194(4-5):743-4.
CNS/PNS interfaces constitute cell boundaries, defining territories with different neuronal and glial contents. Despite their potential implications for regenerative medicine, the mechanisms that restrict oligodendrocytes and astrocytes to the CNS and Schwann cells to the PNS are not known in mammals. To investigate the involvement of peripheral glia and myelin in CNS/PNS boundary maintenance, we first studied mutant mice. We found that inactivation of Krox20/Egr2, a master regulatory gene for myelination in Schwann cells, resulted in CNS/PNS boundary transgression by astrocytes and oligodendrocytes, and in myelination of nerve root axons by oligodendrocytes. In contrast, no such migration was observed in mice with the Trembler(J) mutation, which prevents PNS myelination without affecting Krox20 expression. These findings suggest that CNS/PNS boundary maintenance requires a new Krox20 function independent of myelination control. We also examined a patient with congenital amyelinating neuropathy, whose Schwann cells lack KROX20 protein. Interestingly, the patient's nerve roots were also invaded by oligodendrocytes and astrocytes, indicating that CNS/PNS boundary transgression by central glia can occur in human pathological situations and that the underlying mechanisms are the same as in mutant mice.
中枢神经系统/外周神经系统（CNS/PNS）界面构成细胞边界，界定了具有不同神经元和神经胶质细胞成分的区域。尽管它们对再生医学具有潜在意义，但在哺乳动物中，将少突胶质细胞和星形胶质细胞限制在中枢神经系统以及将施万细胞限制在外周神经系统的机制尚不清楚。为了研究外周神经胶质细胞和髓鞘在CNS/PNS边界维持中的作用，我们首先研究了突变小鼠。我们发现，施万细胞髓鞘形成的主要调控基因Krox20/Egr2失活，导致星形胶质细胞和少突胶质细胞越过CNS/PNS边界，并且少突胶质细胞对神经根轴突进行髓鞘形成。相比之下，在患有Trembler(J)突变的小鼠中未观察到这种迁移，该突变可阻止外周神经系统髓鞘形成而不影响Krox20表达。这些发现表明，CNS/PNS边界维持需要一种独立于髓鞘形成控制的新的Krox20功能。我们还检查了一名患有先天性无髓鞘性神经病的患者，其施万细胞缺乏KROX20蛋白。有趣的是，该患者的神经根也被少突胶质细胞和星形胶质细胞侵入，表明在人类病理情况下，中枢神经胶质细胞可越过CNS/PNS边界，并且其潜在机制与突变小鼠相同。
