Hagihara K, Watanabe K, Chun J, Yamaguchi Y
The Burnham Institute, La Jolla, California 92037, USA.
Dev Dyn. 2000 Nov;219(3):353-67. doi: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1059>3.0.CO;2-#.
FGF2 is a crucial mitogen for neural precursor cells in the developing cerebral cortex. Heparan sulfate proteoglycans (HSPGs) are thought to play a role in cortical neurogenesis by regulating the action of FGF2 on neural precursor cells. In this article, we present data indicating that glypican-4 (K-glypican), a GPI-anchored cell surface HSPG, is involved in these processes. In the developing mouse brain, glypican-4 mRNA is expressed predominantly in the ventricular zone of the telencephalon. Neither the outer layers of the telencephalic wall nor the ventricular zone of other parts of the developing brain express significant levels of glypican-4, with the exception of the ventricular zone of the tectum. In cultures of E13 rat cortical precursor cells, glypican-4 is expressed in cells immunoreactive for nestin and the D1.1 antigen, markers of neural precursor cells. Glypican-4 expression was not detected in early postmitotic or fully differentiated neurons. Recombinant glypican-4 produced in immortalized neural precursor cells binds FGF2 through its heparan sulfate chains and suppressed the mitogenic effect of FGF2 on E13 cortical precursor cells. The spatiotemporal expression pattern of glypican-4 in the developing cerebral wall significantly overlaps with that of FGF2. These results suggest that glypican-4 plays a critical role in the regulation of FGF2 action during cortical neurogenesis.
成纤维细胞生长因子2（FGF2）是发育中的大脑皮层神经前体细胞的关键促有丝分裂原。硫酸乙酰肝素蛋白聚糖（HSPG）被认为通过调节FGF2对神经前体细胞的作用在皮层神经发生中发挥作用。在本文中，我们提供的数据表明，糖基磷脂酰肌醇（GPI）锚定的细胞表面HSPG——磷脂酰肌醇蛋白聚糖4（K-磷脂酰肌醇蛋白聚糖）参与了这些过程。在发育中的小鼠大脑中，磷脂酰肌醇蛋白聚糖4 mRNA主要在端脑的脑室区表达。端脑壁的外层以及发育中大脑其他部位的脑室区均未表达显著水平的磷脂酰肌醇蛋白聚糖4，但顶盖的脑室区除外。在E13大鼠皮质前体细胞培养物中，磷脂酰肌醇蛋白聚糖4在对巢蛋白和D1.1抗原呈免疫反应的细胞中表达，巢蛋白和D1.1抗原是神经前体细胞的标志物。在有丝分裂后早期或完全分化的神经元中未检测到磷脂酰肌醇蛋白聚糖4的表达。永生化神经前体细胞产生的重组磷脂酰肌醇蛋白聚糖4通过其硫酸乙酰肝素链结合FGF2，并抑制FGF2对E13皮质前体细胞的促有丝分裂作用。磷脂酰肌醇蛋白聚糖4在发育中的脑壁中的时空表达模式与FGF2的时空表达模式显著重叠。这些结果表明，磷脂酰肌醇蛋白聚糖4在皮层神经发生过程中对FGF2作用的调节中起关键作用。
