Gli3 is required for maintenance and fate specification of cortical progenitors.
Gli3 is required for maintenance and fate specification of cortical progenitors.
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DOI：
10.1523/jneurosci.4892-10.2011
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发表时间：
2011-04-27
期刊：
影响因子：
--
通讯作者：
Ahn S
中科院分区：
文献类型：
--
作者：
Wang H;Ge G;Uchida Y;Luu B;Ahn S
Gli3是Hedgehog(HH)途径中的三个脊椎动物Gli转录因子之一，在没有HH信号的情况下被加工成抑制子形式(Gli3R)，是该途径的主要负转导子。尽管Gli3在胚胎模式中的作用已经被广泛研究，但它在皮质神经发生中的作用，特别是在调节神经前体细胞增殖和细胞命运指定方面的作用，在很大程度上是未知的。为了绕过Gli3缺失导致的花纹缺陷，我们在小鼠完成花纹后有条件地删除了Gli3。我们来自出生测定和宫内电穿孔实验的结果表明，Gli3，特别是Gli3R，对于指定按照刻板印象的时间顺序产生的皮质神经元的命运至关重要。此外，Gli3是维持活跃的细胞周期中的皮质祖细胞所必需的，这表明细胞在神经发生过程中关闭Gli3的表达可能会获得分化状态。
Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role of Gli3 in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. In order to bypass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning is complete in mouse. Our results from birthdating and in utero electroporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover, Gli3 is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off Gli3 expression during neurogenesis.