Skalecka Agnieszka, Liszewska Ewa, Bilinski Robert, Gkogkas Christos, Khoutorsky Arkady, Malik Anna R, Sonenberg Nahum, Jaworski Jacek
International Institute of Molecular and Cell Biology, 4 Ks. Trojdena St, Warsaw, 02-109, Poland.
Département De Mathématiques, Collège Montmorency, 475 Boulevard De L'Avenir, Laval, Quebec, H7N 5H9, Canada.
Dev Neurobiol. 2016 Dec;76(12):1308-1327. doi: 10.1002/dneu.22392. Epub 2016 Apr 7.
Neurogenesis is the process of neuron generation, which occurs not only during embryonic development but also in restricted niches postnatally. One such region is called the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb (OB). Neurons that are born postnatally migrate through more complex territories and integrate into fully functional circuits. Therefore, differences in the differentiation of embryonic and postnatally born neurons may exist. Dendritogenesis is an important process for the proper formation of future neuronal circuits. Dendritogenesis in embryonic neurons cultured in vitro was shown to depend on the mammalian target of rapamycin (mTOR). Still unknown, however, is whether mTOR could regulate the dendritic arbor morphology of SVZ-derived postnatal OB neurons under physiological conditions in vivo. The present study used in vitro cultured and differentiated SVZ-derived neural progenitors and found that both mTOR complex 1 and mTOR complex 2 were required for the dendritogenesis of SVZ-derived neurons. Furthermore, using a combination of in vivo electroporation of neural stem cells in the SVZ and genetic and pharmacological inhibition of mTOR, it was found that mTOR was crucial for the growth of basal and apical dendrites in postnatally born OB neurons under physiological conditions and contributed to the stabilization of their basal dendrites. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1308-1327, 2016.
神经发生是神经元生成的过程,它不仅发生在胚胎发育期间,也发生在出生后的特定微环境中。其中一个这样的区域称为脑室下区(SVZ),它能产生嗅球(OB)中的新神经元。出生后产生的神经元会通过更复杂的区域迁移并整合到功能完备的神经回路中。因此,胚胎期和出生后产生的神经元在分化上可能存在差异。树突形成是未来神经回路正常形成的一个重要过程。体外培养的胚胎神经元中的树突形成被证明依赖于雷帕霉素的哺乳动物靶点(mTOR)。然而,mTOR在体内生理条件下是否能调节源自SVZ的出生后OB神经元的树突形态仍不清楚。本研究使用体外培养并分化的源自SVZ的神经祖细胞,发现mTOR复合体1和mTOR复合体2都是源自SVZ的神经元树突形成所必需的。此外,通过在SVZ对神经干细胞进行体内电穿孔以及对mTOR进行基因和药理学抑制相结合的方法,发现mTOR在生理条件下对出生后OB神经元的基底和顶端树突的生长至关重要,并有助于其基底树突的稳定。© 2016威利期刊公司。《发育神经生物学》76: 1308 - 1327, 2016。