The role of foxg1 in the development of neural stem cells of the olfactory epithelium.

The role of foxg1 in the development of neural stem cells of the olfactory epithelium.
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DOI:
10.1111/j.1749-6632.2009.04372.x
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发表时间:
2009-07
影响因子:
5.2
通讯作者:
Calof AL
Calof AL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kawauchi S;Santos R;Kim J;Hollenbeck PL;Murray RC;Calof AL

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小鼠的嗅觉上皮 (OE) 是研究神经干细胞生物学原理的绝佳模型系统,因为它具有明确的神经元谱系和终生再生的能力。为了研究 OE 中干细胞调节的分子机制,我们重点关注 Foxg1,也称为脑因子 1,它是 Forkhead 转录因子家族的成员。 Foxg1−/− 小鼠在出生时表现出 OE 的主要缺陷,表明 Foxg1 在 OE 发育中起着重要作用。我们发现 Foxg1 在 OE 基底区室中的细胞中表达,这是已知 OE 干细胞和祖细胞所在的位置。由于已知 FoxG1 在端脑发育过程中调节神经祖细胞的增殖,因此我们在原发性 OE 神经发生过程中对表达 Sox2 的神经干细胞进行了 BrdU 脉冲追踪。我们发现在 Foxg1−/− OE 中保留 BrdU 的表达 Sox2 的细胞百分比是野生型的两倍,这表明在缺乏 Foxg1 的情况下这些细胞的发育被延迟和/或停止。我们的研究结果表明,OE 中表达 Sox2 的神经干细胞的增殖和/或随后的分化受到 Foxg1 的调节。
The olfactory epithelium (OE) of the mouse is an excellent model system for studying principles of neural stem cell biology because of its well-defined neuronal lineage and its ability to regenerate throughout life. To approach the molecular mechanisms of stem cell regulation in the OE, we have focused on Foxg1, also known as brain factor-1, which is a member of the Forkhead transcription factor family. Foxg1−/− mice show major defects in the OE at birth, suggesting that Foxg1 plays an important role in OE development. We find that Foxg1 is expressed in cells within the basal compartment of the OE, the location where OE stem and progenitor are known to reside. Since FoxG1 is known to regulate proliferation of neuronal progenitor cells during telencephalon development, we performed BrdU pulse-chase of Sox2-expressing neural stem cells during primary OE neurogenesis. We found the percentage of Sox2-expressing cells that retained BrdU was twice as high in Foxg1−/− OE as in wildtypes, suggesting that these cells are delayed and/or halted in their development in the absence of Foxg1. Our findings suggest that the proliferation and/or subsequent differentiation of Sox2-expressing neural stem cells in the OE are regulated by Foxg1.
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