Maekawa Motoko, Takashima Noriko, Arai Yoko, Nomura Tadashi, Inokuchi Kaoru, Yuasa Shigeki, Osumi Noriko
Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research (CTAAR), Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Genes Cells. 2005 Oct;10(10):1001-14. doi: 10.1111/j.1365-2443.2005.00893.x.
Neurogenesis is crucial for brain formation and continues to take place in certain regions of the postnatal brain including the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). Pax6 transcription factor is a key player for patterning the brain and promoting embryonic neurogenesis, and is also expressed in the SGZ. In the DG of wild-type rats, more than 90% of total BrdU-incorporated cells expressed Pax6 at 30 min time point after BrdU injection. Moreover, approximately 60% of Pax6+ cells in the SGZ exhibited as GFAP+ cells with a radial glial phenotype and about 30% of Pax6+ cells exhibited as PSA-NCAM+ cells in clusters. From BrdU labeling for 3 days, we found that cell proliferation was 30% decreased at postnatal stages in Pax6-deficient rSey2/+ rat. BrdU pulse/chase experiments combined with marker staining revealed that PSA-NCAM+ late progenitor cells increased at the expense of GFAP+ early progenitors in rSey2/+ rat. Furthermore, expression of Wnt ligands in the SGZ was markedly reduced in rSey2/+ rat. Taken all together, an appropriate dosage of Pax6 is essential for production and maintenance of the GFAP+ early progenitor cells in the postnatal hippocampal neurogenesis.
神经发生对大脑形成至关重要,并在出生后大脑的某些区域持续发生,包括海马齿状回(DG)的颗粒下区(SGZ)。Pax6转录因子是大脑模式形成和促进胚胎神经发生的关键因子,也在SGZ中表达。在野生型大鼠的DG中,在注射BrdU后30分钟时间点,超过90%的总BrdU掺入细胞表达Pax6。此外,SGZ中约60%的Pax6+细胞表现为具有放射状胶质细胞表型的GFAP+细胞,约30%的Pax6+细胞表现为成簇的PSA-NCAM+细胞。通过对BrdU进行3天标记,我们发现Pax6缺陷型rSey2/+大鼠在出生后阶段细胞增殖减少了30%。BrdU脉冲/追踪实验结合标记染色显示,在rSey2/+大鼠中,PSA-NCAM+晚期祖细胞增加,而GFAP+早期祖细胞减少。此外,rSey2/+大鼠SGZ中Wnt配体的表达明显降低。综上所述,适当剂量的Pax6对于出生后海马神经发生中GFAP+早期祖细胞的产生和维持至关重要。