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Ephrin signalling controls brain size by regulating apoptosis of neural progenitors

机译:Ephrin信号传导通过调节神经祖细胞的凋亡来控制大脑大小

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Mechanisms controlling brain size include the regulation of neural progenitor cell proliferation, differentiation, survival and migration(1,2). Here we show that ephrin-A/EphA receptor signalling plays a key role in controlling the size of the mouse cerebral cortex by regulating cortical progenitor cell apoptosis. In vivo gain of EphA receptor function, achieved through ectopic expression of ephrin-A5 in early cortical progenitors expressing EphA7, caused a transient wave of neural progenitor cell apoptosis, resulting in premature depletion of progenitors and a subsequent dramatic decrease in cortical size. In vitro treatment with soluble ephrin-A ligands similarly induced the rapid death of cultured dissociated cortical progenitors in a caspase-3-dependent manner, thereby confirming a direct effect of ephrin/Eph signalling on apoptotic cascades. Conversely, in vivo loss of EphA function, achieved through EphA7 gene disruption, caused a reduction in apoptosis occurring normally in forebrain neural progenitors, resulting in an increase in cortical size and, in extreme cases, exencephalic forebrain overgrowth. Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors.
机译:控制大脑大小的机制包括调节神经祖细胞的增殖,分化,存活和迁移(1,2)。在这里我们显示,ephrin-A / EphA受体信号传导通过调节皮质祖细胞凋亡在控制小鼠大脑皮层的大小中起关键作用。通过在表达EphA7的早期皮质祖细胞中异位表达ephrin-A5来实现体内EphA受体功能的获得,引起神经祖细胞凋亡的短暂波动,导致祖细胞过早耗尽,随后皮质大小急剧减少。可溶性ephrin-A配体的体外处理类似地以caspase-3依赖的方式诱导了培养的离解的皮质祖细胞的快速死亡,从而证实了ephrin / Eph信号传导对凋亡级联反应的直接作用。相反,体内通过EphA7基因破坏而导致的EphA功能丧失导致正常情况下前脑神经祖细胞凋亡的减少,导致皮质大小增加,在极端情况下,脑前脑过度生长。总之,这些结果将ephrin / Eph信号转导为凋亡的生理触发,可以通过调节神经祖细胞的数量来改变大脑的大小和形状。

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