Lateral cortical Cdca7 expression levels are regulated by Pax6 and influence the production of intermediate progenitors.
Lateral cortical Cdca7 expression levels are regulated by Pax6 and influence the production of intermediate progenitors.
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DOI：
10.1186/s12868-017-0365-0
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发表时间：
2017-06-05
期刊：
影响因子：
2.4
通讯作者：
Price DJ
中科院分区：
文献类型：
--
作者：
Huang YT;Mason JO;Price DJ
我们研究了转录因子Pax 6对Cdca 7（细胞分裂周期相关7）表达的调控是否有助于Pax 6在皮质生成过程中的细胞作用。Cdca 7在皮质生成过程中介导Pax 6作用的功能尚未研究。Pax 6由胚胎皮质神经上皮的脑室区中的放射状胶质祖细胞表达，其中它是脑室下区中表达Tbr 2的中间祖细胞的正常补体的发育所需的。Pax 6的表达水平在整个心室区分级，横向水平最高，其中在皮质生成的早期阶段以最大数量产生表达Tbr 2的祖细胞。我们使用原位杂交和免疫组织化学来分析野生型和Pax 6 −/−胚胎皮质组织中Cdca 7和Pax 6的表达模式。在每个基因型中，我们定量比较了两个基因在几个年龄段的分级表达。为了测试Cdca 7在外侧皮质细胞中表达的缺陷是否可能导致Pax 6丢失引起的该区域的细胞缺陷，我们将Cdca 7表达载体电穿孔到野生型外侧皮质中，并检查对Tbr 2表达细胞产生的影响。我们发现，Cdca 7与Pax 6在皮质祖细胞中共表达，与Pax 6的水平相反。最低水平的Cdca 7被发现在外侧皮质的放射状胶质祖细胞，其中Pax 6水平最高。在腹侧端脑中发现较高水平的Cdca 7，其中Pax 6水平较低。Pax 6的缺失导致外侧皮质中Cdca 7表达增加。将正常外侧皮质祖细胞中的Cdca 7升高至接近腹侧端脑中通常发现的水平，降低了外侧皮质形成早期Tbr 2表达细胞的产生。我们的研究结果表明，Pax 6通常抑制Cdca 7在侧皮质的表达，并在该地区的细胞中的Cdca 7的抑制是必要的Tbr 2表达的中间祖细胞的正常补体的生产。
We studied whether regulation of Cdca7 (Cell division cycle associated 7) expression by transcription factor Pax6 contributes to Pax6’s cellular actions during corticogenesis. The function of Cdca7 in mediating Pax6’s effects during corticogenesis has not been explored. Pax6 is expressed by radial glial progenitors in the ventricular zone of the embryonic cortical neuroepithelium, where it is required for the development of a normal complement of Tbr2-expressing intermediate progenitor cells in the subventricular zone. Pax6’s expression levels are graded across the ventricular zone, with highest levels laterally where Tbr2-expressing progenitors are generated in greatest numbers at early stages of corticogenesis. We used in situ hybridization and immunohistochemistry to analyse patterns of Cdca7 and Pax6 expression in cortical tissue from wild-type and Pax6 −/− embryos. In each genotype we compared the graded expression of the two genes quantitatively at several ages. To test whether defects in Cdca7 expression in lateral cortical cells might contribute to the cellular defects in this region caused by Pax6 loss, we electroporated a Cdca7 expression vector into wild-type lateral cortex and examined the effect on the production of Tbr2-expressing cells. We found that Cdca7 is co-expressed with Pax6 in cortical progenitors, at levels opposite to those of Pax6. Lowest levels of Cdca7 are found in the radial glial progenitors of lateral cortex, where Pax6 levels are highest. Higher levels of Cdca7 are found in ventral telencephalon, where Pax6 levels are low. Loss of Pax6 causes Cdca7 expression to increase in the lateral cortex. Elevating Cdca7 in normal lateral cortical progenitors to levels close to those normally found in ventral telencephalon reduces their production of Tbr2-expressing cells early in lateral cortical formation. Our results suggest that Pax6 normally represses Cdca7 expression in the lateral cortex and that repression of Cdca7 in cells of this region is required for their production of a normal complement of Tbr2-expressing intermediate progenitors.