VIB Center for the Biology of Disease, KULeuven Center for Human Genetics, Leuven, Belgium.
EMBO J. 2012 Apr 18;31(8):1893-903. doi: 10.1038/emboj.2012.41. Epub 2012 Feb 21.
The precise polarization and orientation of developing neurons is essential for the correct wiring of the brain. In pyramidal excitatory neurons, polarization begins with the sprouting of opposite neurites, which later define directed migration and axo-dendritic domains. We here show that endogenous N-cadherin concentrates at one pole of the newborn neuron, from where the first neurite subsequently emerges. Ectopic N-cadherin is sufficient to favour the place of appearance of the first neurite. The Golgi and centrosome move towards this newly formed morphological pole in a second step, which is regulated by PI3K and the actin/microtubule cytoskeleton. Moreover, loss of function experiments in vivo showed that developing neurons with a non-functional N-cadherin misorient their cell axis. These results show that polarization of N-cadherin in the immediate post-mitotic stage is an early and crucial mechanism in neuronal polarity.
发育中的神经元的精确极化和定向对于大脑的正确布线至关重要。在锥体兴奋性神经元中，极化始于相反神经突起的发芽，随后确定定向迁移和轴突树突域。我们在这里表明，内源性 N-钙粘蛋白集中在新神经元的一个极上，随后第一个神经突起从那里出现。异位 N-钙粘蛋白足以促进第一个神经突起出现的位置。高尔基氏体和中心体在第二步向这个新形成的形态极移动，这一步受 PI3K 和肌动蛋白/微管细胞骨架调节。此外，体内功能丧失实验表明，具有非功能 N-钙粘蛋白的发育神经元会使它们的细胞轴错位。这些结果表明，N-钙粘蛋白在有丝分裂后即刻的极化是神经元极性的早期和关键机制。
