Papachristou Panagiotis, Dyberg Cecilia, Lindqvist Maria, Horn Zachi, Ringstedt Thomas
Neonatal Research Unit, Astrid Lindgren Children׳s Hospital, Q2:07, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Neonatal Research Unit, Astrid Lindgren Children׳s Hospital, Q2:07, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Brain Res. 2014 Aug 12;1576:27-34. doi: 10.1016/j.brainres.2014.06.015. Epub 2014 Jun 19.
Wnt/beta-catenin signaling plays an important role in neural development, instructing both progenitor cell division and differentiation. During early corticogenesis, Wnt7b is expressed in a restricted expression pattern in the ventricular zone progenitor cells. However, its influence on progenitor cell behavior has not been fully studied. We report that transgenic overexpression of Wnt7b in neural progenitor cells impairs neuronal differentiation and the development of forebrain structures at embryonic day 10.5 (E10.5). This was accompanied by a decreased expression of T-domain transcription factors Tbr1 and Tbr2, in both progenitor cells and post-mitotic neurons. However, proliferation, apoptosis and the overall proportion of pax6(+) neural progenitor cells were similar to wild-type litter mates. These results suggest that Wnt signaling may affect early neural progenitor differentiation by regulating the expression of pro-neural transcription factors.
Wnt/β-连环蛋白信号通路在神经发育中起重要作用,指导祖细胞的分裂和分化。在早期皮质发生过程中,Wnt7b在脑室区祖细胞中以受限的表达模式表达。然而,其对祖细胞行为的影响尚未得到充分研究。我们报告,在神经祖细胞中Wnt7b的转基因过表达会损害胚胎第10.5天(E10.5)时的神经元分化和前脑结构的发育。这伴随着T结构域转录因子Tbr1和Tbr2在祖细胞和有丝分裂后神经元中的表达降低。然而,增殖、凋亡以及pax6(+)神经祖细胞的总体比例与野生型同窝仔相似。这些结果表明,Wnt信号通路可能通过调节神经前体转录因子的表达来影响早期神经祖细胞的分化。