Capaldo Emily, Iulianella Angelo
Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Life Science Research Institute, Nova Scotia, Canada.
Dev Dyn. 2016 Aug;245(8):881-96. doi: 10.1002/dvdy.24418. Epub 2016 Jun 13.
The rhombic lip (RL), a germinal zone in the developing hindbrain, gives rise to all of the excitatory neurons of the cerebellum. It is presently unclear what factors distinguish between RL progenitor pools and play a role in differentiating the multiple cell types that arise from this region. The transcription factor Cux2 has been shown to play important roles in proliferation and differentiation of distinct neuronal populations during embryogenesis, but its role in cerebellar fate restriction is unknown.
Through expression analysis and genetic fate mapping studies we show that Cux2 is expressed in the RL of the fetal brain and is restricted to a pool of cerebellar granule cell precursors and unipolar brush cells. This restriction was remarkably specific because regardless of the timing of Cux2 reporter gene activation in the RL, only granule cell layer derivatives were labeled. However, the overexpression of Cux2 in naïve hindbrain tissue was insufficient to force progenitor cells to adopt a granule cell fate.
Our results suggest that Cux2 delineates the pool of cerebellar granule cell layer progenitors from other RL and ventricular zone derivatives, and plays a role in fate restricting, but not differentiating, this population. Developmental Dynamics 245:881-896, 2016. © 2016 Wiley Periodicals, Inc.
菱唇(RL)是发育中的后脑生发区,可产生小脑的所有兴奋性神经元。目前尚不清楚哪些因素区分了RL祖细胞群,并在分化源自该区域的多种细胞类型中发挥作用。转录因子Cux2已被证明在胚胎发育过程中不同神经元群体的增殖和分化中起重要作用,但其在小脑命运限制中的作用尚不清楚。
通过表达分析和遗传命运图谱研究,我们发现Cux2在胎儿脑的RL中表达,并局限于小脑颗粒细胞前体和单极刷细胞群。这种限制非常特异,因为无论Cux2报告基因在RL中何时激活,只有颗粒细胞层衍生物被标记。然而,在幼稚后脑组织中过表达Cux2不足以迫使祖细胞采用颗粒细胞命运。
我们的结果表明,Cux2将小脑颗粒细胞层祖细胞群与其他RL和脑室区衍生物区分开来,并在命运限制而非分化该群体中发挥作用。《发育动力学》245:881 - 896,2016年。©2016威利期刊公司。