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The Corticofugal Neuron-Associated Genes ROBO1, SRGAP1, and CTIP2 Exhibit an Anterior to Posterior Gradient of Expression in Early Fetal Human Neocortex Development

机译:皮质胎儿神经元相关基因ROBO1,SRGAP1和CTIP2在早期胎儿人类新皮层发育中表现出前向后梯度表达

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摘要

Developing neocortical progenitors express transcription factors in gradients that induce programs of region-specific gene expression. Our previous work identified anteriorly upregulated expression gradients of a number of corticofugal neuron-associated gene probe sets along the anterior–posterior axis of the human neocortex (8-12 postconceptional weeks [PCW]). Here, we demonstrate by real-time polymerase chain reaction, in situ hybridization and immunohistochemistry that 3 such genes, ROBO1, SRGAP1, and CTIP2 are highly expressed anteriorly between 8-12 PCW, in comparison with other genes (FEZF2, SOX5) expressed by Layer V, VI, and subplate neurons. All 3 were prominently expressed by early postmitotic neurons in the subventricular zone, intermediate zone, and cortical plate (CP) from 8 to 10 PCW. Between 12 and 15 PCW expression patterns for ER81 and SATB2 (Layer V), TBR1 (Layer V/VI) and NURR1 (Layer VI) revealed Layer V forming. By 15 PCW, ROBO1 and SRGAP1 expression was confined to Layer V, whereas CTIP2 was expressed throughout the CP anteriorly. We observed ROBO1 and SRGAP1 immunoreactivity in medullary corticospinal axons from 11 PCW onward. Thus, we propose that the coexpression of these 3 markers in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation.
机译:发育中的新皮层祖细胞以梯度表达转录因子,可诱导区域特异性基因表达程序。我们以前的工作确定了沿人类新皮层的前后轴(受孕后8-12周),许多与皮质原发性神经元相关的基因探针集的表达上调。在这里,我们通过实时聚合酶链反应,原位杂交和免疫组化实验证明,与其他基因(FEZF2,SOX5)相比,ROBO1,SRGAP1和CTIP2这3个基因在8-12 PCW之间高度表达V,VI和亚板神经元。所有3种都在8至10 PCW的心室下区域,中间区域和皮质板(CP)中由早期有丝分裂后神经元显着表达。在ER81和SATB2(第V层)的12至15个PCW表达模式之间,TBR1(第V / VI层)和NURR1(第VI层)显示了第V层的形成。通过15 PCW,ROBO1和SRGAP1的表达被限制在第V层,而CTIP2在整个CP的前部表达。我们从11个PCW开始观察到了髓质皮质脊髓轴突中的ROBO1和SRGAP1免疫反应。因此,我们建议在前皮层中这3种标记物的共表达可能标志着人类运动皮层的早期位置,包括其皮质脊髓投射神经元,从而允许对其早期分化进行进一步的研究。

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