Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis.

Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis.
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DOI:
10.1371/journal.pone.0003859
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发表时间:
2008
期刊:
影响因子:
3.7
通讯作者:
Moore, Adrian W.
Moore, Adrian W.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kinameri, Emi;Inoue, Takashi;Aruga, Jun;Imayoshi, Itaru;Kageyama, Ryoichiro;Shimogori, Tomomi;Moore, Adrian W.

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功能性中枢神经系统(CNS)的建立和维持需要高度协调的神经祖细胞增殖、细胞周期退出和分化过程。一个进化保守的程序组成的Notch信号传导介导的基本螺旋环抑制(bHLH)转录因子活性是必要的神经祖细胞的特征和神经发生的进展的维护,然而,其他球员在哺乳动物中枢神经系统的神经规范仍然在很大程度上未知。在果蝇中,我们最近的特点哈姆雷特,一个转录因子,介导的Notch信号和神经细胞的命运。哈姆雷特是Prdm(PRDI-BF 1 and RIZ homologous domain containing)原癌基因转录因子家族的成员,在本研究中我们报道了Prdm家族中的多个基因(Prdm 6,8,12,13和16)在发育中的小鼠CNS中以空间和时间受限的方式表达。在发育中的脊髓Prdm 8,12和13在精确的神经元祖细胞区中表达,这表明它们可以指定离散的神经元亚型。在开发端脑Prdm 12和16在脑室区中表达的横向到内侧分级的方式,和Prdm 8有丝分裂后的神经元中的互补域中表达。在出生后的大脑中,Prdm 8还显示出在皮质层2/3和4、海马和杏仁核中的受限表达。为了进一步阐明Prdm 8和16在端脑发育中的作用,我们分析了这些因子与Notch信号传导的bHLH Hes(Hairy和增强子分裂同源物)效应子之间的关系。在Hes空端脑神经分化增强,Prdm 8表达上调,Prdm 16表达下调;相反,在子宫内电穿孔Hes 1到发育中的端脑上调Prdm 16的表达。我们的数据表明,Prdm基因受Notch-Hes通路的调控,并代表了控制神经类规范和哺乳动物CNS神经发生的顺序进展的强有力的候选人。
Establishment and maintenance of a functional central nervous system (CNS) requires a highly orchestrated process of neural progenitor cell proliferation, cell cycle exit, and differentiation. An evolutionary conserved program consisting of Notch signalling mediated by basic Helix-Loop-Helix (bHLH) transcription factor activity is necessary for both the maintenance of neural progenitor cell character and the progression of neurogenesis; however, additional players in mammalian CNS neural specification remain largely unknown. In Drosophila we recently characterized Hamlet, a transcription factor that mediates Notch signalling and neural cell fate. Hamlet is a member of the Prdm (PRDI-BF1 and RIZ homology domain containing) proto-oncogene transcription factor family, and in this study we report that multiple genes in the Prdm family (Prdm6, 8, 12, 13 and 16) are expressed in the developing mouse CNS in a spatially and temporally restricted manner. In developing spinal cord Prdm8, 12 and 13 are expressed in precise neuronal progenitor zones suggesting that they may specify discrete neuronal subtypes. In developing telencephalon Prdm12 and 16 are expressed in the ventricular zone in a lateral to medial graded manner, and Prdm8 is expressed in a complementary domain in postmitotic neurons. In postnatal brain Prdm8 additionally shows restricted expression in cortical layers 2/3 and 4, the hippocampus, and the amygdala. To further elucidate roles of Prdm8 and 16 in the developing telencephalon we analyzed the relationship between these factors and the bHLH Hes (Hairy and enhancer of split homolog) effectors of Notch signalling. In Hes null telencephalon neural differentiation is enhanced, Prdm8 expression is upregulated, and Prdm16 expression is downregulated; conversely in utero electroporation of Hes1 into the developing telencephalon upregulates Prdm16 expression. Our data demonstrate that Prdm genes are regulated by the Notch-Hes pathway and represent strong candidates to control neural class specification and the sequential progression of mammalian CNS neurogenesis.
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