Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development.

Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development.
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DOI:
10.1111/j.1460-9568.2008.06475.x
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发表时间:
2008-10
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Clowry GJ
Clowry GJ
中科院分区:
其他
文献类型:
--
作者:
Bayatti N;Sarma S;Shaw C;Eyre JA;Vouyiouklis DA;Lindsay S;Clowry GJ

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转录因子Emx2和Pax6在发育中的啮齿动物新皮层的增殖区表达,其表达梯度相互作用决定了尾侧和吻侧的身份。Pax6也参与皮质神经发生,由径向胶质祖细胞表达,产生的细胞也依次表达Tbr2、NeuroD和Tbr1,这些基因暂时位于Pax6的下游。在本研究中,我们采用原位杂交技术分析了EMX2、PAX6、TBR2、NEUROD和TBR1 mRNA在妊娠后8 - 12周(PCW)发育中的人皮层中的表达。EMX2 mRNA在脑室(VZ)和脑室下区(SVZ)表达,但也在皮质板中表达,这与啮齿动物不同。然而,在所有研究年龄的啮齿动物中,表达梯度相似。PAX6 mRNA的表达仅限于VZ和SVZ。在8 PCW时,PAX6在喙侧高度表达,但在尾侧表达较少,正如在啮齿动物中看到的那样,然而这种梯度在皮质发生的早期消失了,到9 PCW。与啮齿类动物相比,TBR2、NEUROD和TBR1 mRNA的限制性室特异性表达较少,其表达梯度与PAX6在9 PCW之前的表达梯度相似。TBR2的梯度消失时间为10 PCW, NEUROD和TBR1的梯度消失时间为12 PCW。这些数据支持了最近的报道,即EMX2而不是PAX6更直接地参与了实现,强调了对人类发育的分析比对啮齿动物的研究具有更好的时空分辨率。
The transcription factors Emx2 and Pax6 are expressed in the proliferating zones of the developing rodent neocortex, and gradients of expression interact in specifying caudal and rostral identities. Pax6 is also involved in corticoneurogenesis, being expressed by radial glial progenitors that give rise to cells that also sequentially express Tbr2, NeuroD and Tbr1, genes temporally downstream of Pax6. In this study, using in situ hybridization, we analysed the expression of EMX2, PAX6, TBR2, NEUROD and TBR1 mRNA in the developing human cortex between 8 and 12 postconceptional weeks (PCW). EMX2 mRNA was expressed in the ventricular (VZ) and subventricular zones (SVZ), but also in the cortical plate, unlike in the rodent. However, gradients of expression were similar to that of the rodent at all ages studied. PAX6 mRNA expression was limited to the VZ and SVZ. At 8 PCW, PAX6 was highly expressed rostrally but less so caudally, as has been seen in the rodent, however this gradient disappeared early in corticogenesis, by 9 PCW. There was less restricted compartment-specific expression of TBR2, NEUROD and TBR1 mRNA than in the rodent, where the gradients of expression were similar to that of PAX6 prior to 9 PCW. The gradient disappeared for TBR2 by 10 PCW, and for NEUROD and TBR1 by 12 PCW. These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents.
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