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A Sharp Cadherin-6 Gene Expression Boundary in the Developing Mouse Cortical Plate Demarcates the Future Functional Areal Border

机译:发育中的小鼠皮质板中的锋利的Cadherin-6基因表达边界划定了未来的功能区域边界

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摘要

The mammalian cerebral cortex can be tangentially subdivided into tens of functional areas with distinct cyto-architectures and neural circuitries; however, it remains elusive how these areal borders are genetically elaborated during development. Here we establish original bacterial artificial chromosome transgenic mouse lines that specifically recapitulate cadherin-6 (Cdh6) mRNA expression profiles in the layer IV of the somatosensory cortex and by detailing their cortical development, we show that a sharp Cdh6 gene expression boundary is formed at a mediolateral coordinate along the cortical layer IV as early as the postnatal day 5 (P5). By further applying mouse genetics that allows rigid cell fate tracing with CreERT2 expression, it is demonstrated that the Cdh6 gene expression boundary set at around P4 eventually demarcates the areal border between the somatosensory barrel and limb field at P20. In the P6 cortical cell pellet culture system, neurons with Cdh6 expression preferentially form aggregates in a manner dependent on Ca2+ and electroporation-based Cdh6 overexpression limited to the postnatal stages perturbs area-specific cell organization in the barrel field. These results suggest that Cdh6 expression in the nascent cortical plate may serve solidification of the protomap for cortical functional areas.
机译:哺乳动物的大脑皮层可被切分为数十个具有不同细胞结构和神经回路的功能区域。然而,在开发过程中如何对这些区域边界进行遗传修饰仍然难以捉摸。在这里,我们建立了原始细菌人工染色体转基因小鼠品系,该小鼠品系专门概括了体感皮层IV层中的钙黏着蛋白6(Cdh6)mRNA表达谱,并通过详细说明它们的皮层发育,我们显示了在C端形成了清晰的Cdh6基因表达边界。早在产后第5天(P5)沿皮质IV层的前外侧坐标。通过进一步应用允许使用CreERT2表达进行刚性细胞命运追踪的小鼠遗传学,证明了在P4附近设置的Cdh6基因表达边界最终在P20处划定了体感桶和肢体场之间的区域边界。在P6皮质细胞沉淀培养系统中,具有Cdh6表达的神经元以依赖Ca 2 + 的方式优先形成聚集体,而基于电穿孔的Cdh6过表达仅限于产后阶段,扰乱了区域中特定于细胞的组织。桶场。这些结果表明,Cdh6在新生皮质板中的表达可能有助于固化皮质功能区的原图。

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