A role for proneural genes in the maturation of cortical progenitor cells
A role for proneural genes in the maturation of cortical progenitor cells
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DOI：
10.1093/cercor/bhj168
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发表时间：
2006-07-01
期刊：
影响因子：
3.7
通讯作者：
Schuurmans, Carol
中科院分区：
文献类型：
--
作者：
Britz, Olivier;Mattar, Pierre;Schuurmans, Carol
我们以前表明，原神经基因Neurogenin 1（Ngn 1）和Ngn 2需要指定新皮层中早期而不是晚期出生的神经元的表型，通过抑制Mash 1（第三种皮层表达的原神经基因）在泛作用。Ngn 1/2特异性活性的精确时间是出乎意料的，因为这些基因在整个皮质发育过程中表达，促使我们寻找后来的功能。在这里，我们发现，Ngn 2和Mash 1的表达在一个动态的方式，获得细胞周期的偏见，非重叠的分布，与未来的基础祖细胞的优先表达，在中期皮质。我们还确定了Ngn 2在后一时期的新功能，表明它需要调节圆锥形祖细胞从脑室区（VZ）到脑室下区的转运。值得注意的是，Ngn 2至少部分地通过Mash 1的抑制来调节祖细胞成熟，因为Mash 1的错误表达强烈增强了祖细胞从VZ的退出。值得注意的是，Mash 1促进祖细胞成熟的能力独立于其重新指定皮质细胞的能力，因此是Mash I的新功能。总之，这些数据支持Ngn 2和Mash 1一起发挥作用以调节发育中的新皮层中祖细胞的带状分布的模型。
We showed previously that the proneural genes Neurogenin1 (Ngn1) and Ngn2 are required to specify the phenotypes of early- and not late-born neurons in the neocortex, acting in pan through repression of Mash1, a third cortically expressed proneural gene. The precise timing of Ngn1/2 specification activity was unexpected given these genes are expressed throughout cortical development, prompting us to search for a later function. Here we reveal that Ngn2 and Mash1 are expressed in a dynamic fashion, acquiring a cell cycle-biased, nonoverlapping distribution, with preferential expression in prospective basal progenitors, during mid corticogenesis. We also identified a new function for Ngn2 during this latter period, demonstrating that it is required to regulate the transit of conical progenitors from the ventricular zone (VZ) to the subventricular zone. Notably, Ngn2 regulates progenitor maturation at least in part through repression of Mash1 as misexpression of Mash1 strongly enhanced progenitor cell exit from the VZ. Significantly, the ability of Mash1 to promote progenitor cell maturation occurred independently of its ability to respecify cortical cells and is thus a novel function for Mash I. Taken together, these data support a model whereby Ngn2 and Mash 1 function together to regulate the zonal distribution of progenitors in the developing neocortex.