prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.
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Notch信号传导下游PRDM1A和OLIG4在神经板边界处调节细胞命运。

DOI:
10.1016/j.ydbio.2011.06.005
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发表时间:
2011-08-15
影响因子:
2.7
通讯作者:
Artinger KB
Artinger KB
中科院分区:
生物学3区
文献类型:
--
作者:
Hernandez-Lagunas L;Powell DR;Law J;Grant KA;Artinger KB

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锌指结构域转录因子prdm1a在神经板边缘细胞(包括神经嵴细胞和roron - beard (RB)感觉神经元)的发育中起着不可或缺的作用。然而,prdm1a功能细胞命运规范的机制尚不清楚。在这里,我们更直接地测试了prdm1a在细胞命运决定中的作用。prdm1a不影响神经板边界的细胞死亡或增殖,而是通过抵消邻近神经元间域olig4的表达来明确影响细胞命运。在prdm1a突变体中,olig4的表达增加,敲低olig4可以挽救prdm1a突变体中减少或消失的神经嵴和RB神经元表型,这表明prdm1a在神经板边界来源的细胞命运中起着允许的作用。此外,在缺乏Notch功能的情况下,prdm1a表达上调,抑制Notch信号传导无法挽救prdm1a突变体。这表明prdm1a在Notch的下游调控神经板边缘的细胞命运,Notch调节神经板边缘祖细胞的总数。
The zinc finger domain transcription factor prdm1a plays an integral role in the development of the neural plate border cell fates, including neural crest cells and Rohon-Beard (RB) sensory neurons. However, the mechanisms underlying prdm1a function cell fate specification is unknown. Here, we test more directly how prdm1a functions in this cell fate decision. Rather than affecting cell death or proliferation at the neural plate border, prdm1a acts explicitly on cell fate specification by counteracting olig4 expression in the neighboring interneuron domain. olig4 expression is expanded in prdm1a mutants and olig4 knockdown can rescue the reduced or abrogated neural crest and RB neuron phenotype in prdm1a mutants, suggesting a permissive role for prdm1a in neural plate border-derived cell fates. In addition, prdm1a expression is upregulated in the absence of Notch function, and inhibiting Notch signaling fails to rescue prdm1a mutants. This suggests that prdm1a functions downstream of Notch in the regulation of cell fate at the neural plate border and that Notch regulates the total number of progenitor cells at the neural plate border.
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