Heins Nico, Malatesta Paolo, Cecconi Francesco, Nakafuku Masato, Tucker Kerry Lee, Hack Michael A, Chapouton Prisca, Barde Yves-Alain, Götz Magdalena
Max-Planck Institute of Neurobiology, Am Klopferspitz 18a, 82152, Planegg-Martinsreid, Munich, Germany.
Nat Neurosci. 2002 Apr;5(4):308-15. doi: 10.1038/nn828.
Radial glial cells, ubiquitous throughout the developing CNS, guide radially migrating neurons and are the precursors of astrocytes. Recent evidence indicates that radial glial cells also generate neurons in the developing cerebral cortex. Here we investigated the role of the transcription factor Pax6 expressed in cortical radial glia. We showed that radial glial cells isolated from the cortex of Pax6 mutant mice have a reduced neurogenic potential, whereas the neurogenic potential of non-radial glial precursors is not affected. Consistent with defects in only one neurogenic lineage, the number of neurons in the Pax6 mutant cortex in vivo is reduced by half. Conversely, retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro. These results demonstrated an important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells.
放射状胶质细胞在整个发育中的中枢神经系统中普遍存在，引导神经元进行径向迁移，并且是星形胶质细胞的前体。最近的证据表明，放射状胶质细胞在发育中的大脑皮层中也能生成神经元。在这里，我们研究了在皮层放射状胶质细胞中表达的转录因子Pax6的作用。我们发现，从Pax6突变小鼠的皮层中分离出的放射状胶质细胞具有降低的神经发生潜能，而非放射状胶质前体细胞的神经发生潜能则不受影响。与仅一个神经发生谱系中的缺陷一致，Pax6突变皮层中体内神经元的数量减少了一半。相反，逆转录病毒介导的Pax6表达即使在体外出生后皮层的星形胶质细胞中也能指导神经发生。这些结果证明了Pax6作为胶质细胞神经发生潜能的内在命运决定因素的重要作用。
