Nature, vol. 435, no.7046
控制大脑大小的机制是发育遗传学、神经学和哺乳动物演化的核心内容。一项新的研究表明,一组被称为ephrins、存在于发育中的大脑中的新的信号因子,能够诱导产生所有神经细胞的前体细胞或干细胞的死亡,从而控制大脑皮层的最终大小。当这种死亡信号增加时,大脑尺寸减小,导致小脑症。当该信号减少时,皮层尺寸增加,导致大脑生长过度。这一发现对于脑病、脑再生和脑癌来说有重要意义。
Ephrin signalling controls brain size by regulating apoptosis of neural progenitors
Mechanisms controlling brain size include the regulation of neural progenitor cell proliferation, differentiation, survival and migration1, 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.
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