Bentley C A, Lee K F
The Salk Institute, La Jolla, California 92037, USA.
J Neurosci. 2000 Oct 15;20(20):7706-15. doi: 10.1523/JNEUROSCI.20-20-07706.2000.
Mice lacking the low-affinity neurotrophin receptor p75 have multiple peripheral neural deficits. Here we examined the developmental nature of these deficiencies. Peripheral axons in p75 -/- embryos were severely stunted and poorly arborized from embryonic day 11.5 (E11.5) to E14.5. In vitro, neurite outgrowth from the dorsal root ganglia was significantly decreased in the p75 -/- embryos at E12.5, suggesting that stunted axonal growth in the embryo may result in part from defects in neurite elongation. Additionally, Schwann cell marker S100beta immunoreactivity was decreased or absent along the growing axons of the ophthalmic branch from the trigeminal ganglia in p75 -/- embryos. Electron microscopy studies of the axons of the trigeminal ganglion at E13.5 revealed that in the p75 mutant embryo, nerve bundles were highly impaired and that coverage of the growing axons by Schwann cell cytoplasm was substantially reduced. In vitro, Schwann cell migration from the dorsal root ganglia was significantly decreased in the p75 -/- embryos at E12.5, suggesting that the lack of S100beta staining and Schwann cell coverage in the p75 mutant results from a deficit in Schwann cell migration. These results provide evidence that p75 is important in the developing embryo for regulating axon growth and arborization and for Schwann cell migration.
缺乏低亲和力神经营养因子受体p75的小鼠存在多种外周神经缺陷。在此,我们研究了这些缺陷的发育本质。从胚胎第11.5天(E11.5)到E14.5,p75基因敲除胚胎中的外周轴突严重发育不良且分支稀少。在体外,E12.5时p75基因敲除胚胎背根神经节的神经突生长显著减少,这表明胚胎中轴突生长发育不良可能部分是由于神经突伸长缺陷所致。此外,在p75基因敲除胚胎中,三叉神经节眼支生长轴突上的雪旺细胞标志物S100β免疫反应性降低或缺失。对E13.5时三叉神经节轴突的电子显微镜研究显示,在p75突变胚胎中,神经束严重受损,雪旺细胞胞质对生长轴突的覆盖显著减少。在体外,E12.5时p75基因敲除胚胎背根神经节的雪旺细胞迁移显著减少,这表明p75突变体中S100β染色缺失和雪旺细胞覆盖不足是由于雪旺细胞迁移缺陷所致。这些结果证明,p75在胚胎发育过程中对调节轴突生长和分支以及雪旺细胞迁移至关重要。