Mutch Christopher A, Funatsu Nobuo, Monuki Edwin S, Chenn Anjen
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
J Neurosci. 2009 Oct 28;29(43):13710-9. doi: 10.1523/JNEUROSCI.3022-09.2009.
The mechanisms underlying the timing of the laminar fate decisions during cortical neurogenesis remain poorly understood. Here we show that beta-catenin signaling in cortical neural precursors can regulate the laminar fate of their daughters. In ventricular zone neural precursors, beta-catenin signaling is higher when deep-layer neurons are being generated and lower when upper-layer neurons are being generated. Overactivation of beta-catenin in cortical precursors midway through corticogenesis increased the relative production of deep-layer neurons, while inhibition of signaling increased the relative production of upper-layer neurons. Furthermore, in late-gestation upper-layer precursors, overactive beta-catenin signaling was able to partially restore production of deep-layer neurons. These observations suggest that increased beta-catenin signaling can reset the timing of cortical precursors to promote the production of deep-layer neurons, while inhibition of beta-catenin signaling advances the timing to promote upper-layer production.
在皮质神经发生过程中，层状命运决定的时间机制仍知之甚少。在这里，我们表明皮质神经前体细胞中的β-连环蛋白信号传导可以调节其后代的层状命运。在脑室区神经前体细胞中，当生成深层神经元时，β-连环蛋白信号传导较高，而当生成上层神经元时，β-连环蛋白信号传导较低。在皮质发生过程中，皮质前体细胞中β-连环蛋白的过度激活增加了深层神经元的相对产量，而信号传导的抑制则增加了上层神经元的相对产量。此外，在妊娠后期的上层前体细胞中，过度活跃的β-连环蛋白信号传导能够部分恢复深层神经元的产生。这些观察结果表明，增加β-连环蛋白信号传导可以重置皮质前体细胞的时间，以促进深层神经元的产生，而抑制β-连环蛋白信号传导则提前时间以促进上层神经元的产生。
