Smith Karen Müller, Ohkubo Yasushi, Maragnoli Maria Elisabetta, Rasin Mladen-Roko, Schwartz Michael L, Sestan Nenad, Vaccarino Flora M
Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nat Neurosci. 2006 Jun;9(6):787-97. doi: 10.1038/nn1705. Epub 2006 May 21.
Midline astroglia in the cerebral cortex develop earlier than other astrocytes through mechanisms that are still unknown. We show that radial glia in dorsomedial cortex retract their apical endfeet at midneurogenesis and translocate to the overlaying pia, forming the indusium griseum. These cells require the fibroblast growth factor receptor 1 (Fgfr1) gene for their precocious somal translocation to the dorsal midline, as demonstrated by inactivating the Fgfr1 gene in radial glial cells and by RNAi knockdown of Fgfr1 in vivo. Dysfunctional astroglial migration underlies the callosal dysgenesis in conditional Fgfr1 knockout mice, suggesting that precise targeting of astroglia to the cortex has unexpected roles in axon guidance. FGF signaling is sufficient to induce somal translocation of radial glial cells throughout the cortex; furthermore, the targeting of astroglia to dorsolateral cortex requires FGFr2 signaling after neurogenesis. Hence, FGFs have an important role in the transition from radial glia to astrocytes by stimulating somal translocation of radial glial cells.
大脑皮质中的中线星形胶质细胞通过尚不清楚的机制比其他星形胶质细胞发育得更早。我们发现，背内侧皮质中的放射状胶质细胞在神经发生中期缩回其顶端终足，并迁移至覆盖的软脑膜，形成海马残体。这些细胞需要成纤维细胞生长因子受体1（Fgfr1）基因才能将其胞体早熟地迁移至背中线，在放射状胶质细胞中使Fgfr1基因失活以及在体内通过RNA干扰敲低Fgfr1均证明了这一点。条件性Fgfr1基因敲除小鼠胼胝体发育不全的基础是星形胶质细胞迁移功能失调，这表明星形胶质细胞精确靶向皮质在轴突导向中具有意想不到的作用。FGF信号足以诱导整个皮质中放射状胶质细胞的胞体迁移；此外，神经发生后星形胶质细胞靶向背外侧皮质需要FGFr2信号。因此，FGF通过刺激放射状胶质细胞的胞体迁移在从放射状胶质细胞向星形胶质细胞的转变中发挥重要作用。
