The spatio-temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development
The spatio-temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development
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DOI：
10.1111/j.1460-9568.2008.06092.x
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Tejedor, Francisco J.
中科院分区：
文献类型：
--
作者：
Hammerle, Barbara;Elizalde, Carina;Tejedor, Francisco J.
人们普遍认为唐氏综合征（DS）的神经系统改变主要是由于发育过程的改变。因此，近年来对DS的大部分研究都集中在影响大脑发育的21号染色体基因上。MNB/DYRK 1A是人类21号染色体上引起最大兴趣的基因之一，由于其与DS中改变的脑功能的关系。虽然一些有趣的实验小鼠模型的DS正在开发中，我们仍然知道很少的Mnb/Dyrk 1A在小鼠大脑发育过程中的表达。在这里，我们报告，Mnb/Dyrk 1A显示一个相当动态的时空表达模式在小鼠中枢神经系统发育。我们的数据表明，Mnb/Dyrk 1A特异性表达在四个连续的发展阶段：在preneurogenic祖细胞的瞬时表达，细胞周期调节的神经祖细胞的表达，在最近出生的神经元的瞬时表达，和持续表达在晚期分化的神经元。我们的研究结果还表明，MNB/DYRK 1A的亚细胞定位，包括其易位到细胞核，是精细调节。因此，MNB/DYRK 1A蛋白激酶可能是神经元发育中偶联顺序事件的分子机制中的关键元件。在发育中的中枢神经系统中的这种丰富的潜在功能库适合于通过使用小鼠实验模型与DS中的神经学改变相关联。
It is widely accepted that the neurological alterations in Down syndrome (DS) are principally due to modifications in developmental processes. Accordingly, a large part of the research on DS in recent years has focused on chromosome 21 genes that influence brain development. MNB/DYRK1A is one of the genes on human chromosome 21 that has raised most interest, due to its relationship with the brain functions that are altered in DS. Although a number of interesting experimental mouse models for DS are being developed, we still know little about the expression of Mnb/Dyrk1A during mouse brain development. Here, we report that Mnb/Dyrk1A displays a rather dynamic spatio-temporal expression pattern during mouse central nervous system development. Our data indicate that Mnb/Dyrk1A is specifically expressed in four sequential developmental phases: transient expression in preneurogenic progenitors, cell cycle-regulated expression in neurogenic progenitors, transient expression in recently born neurones, and persistent expression in late differentiating neurones. Our results also suggest that the subcellular localization of MNB/DYRK1A, including its translocation to the nucleus, is finely regulated. Thus, the MNB/DYRK1A protein kinase could be a key element in the molecular machinery that couples sequential events in neuronal development. This rich repertoire of potential functions in the developing central nervous system is suitable to be linked to the neurological alterations in DS through the use of mouse experimental models.