Osheroff Hilleary, Hatten Mary E
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USA.
Cereb Cortex. 2009 Jul;19 Suppl 1(Suppl 1):i126-34. doi: 10.1093/cercor/bhp034. Epub 2009 Apr 27.
During mammalian corticogenesis a series of transient cell layers establish laminar architectonics. The preplate, which forms from the earliest-generated neurons, separates into the marginal zone and subplate layer. To provide a systematic screen for genes involved in subplate development and function, we screened lines of transgenic mice, generated using bacterial artificial chromosome methodology (GENSAT Project), to identify transgenic lines of mice that express the enhanced green fluorescent protein (EGFP) reporter in preplate neurons destined for the subplate. Gene expression profiling of RNA purified from EGFP-positive neurons identified over 200 genes with enriched expression in future subplate neurons. Major classes of subplate-enriched genes included genes involved in transcriptional processes, cortical development, cell and axon motility, protein trafficking and steroid hormone signaling. Additionally, we identified 10 genes related to degenerative diseases of the cerebral and cerebellar cortex. Cre recombinase-based fate mapping of cells expressing Phosphodiesterase 1c (Pde1c) revealed beta-galactosidase positive cells in the ventricular zone, as well as the subplate, suggesting that subplate neurons and cortical projection neurons may be derived from common progenitors. These experiments therefore reveal genetic markers, which identify subplate neurons from the earliest stages of their development, and genes with enriched expression in subplate neurons during early stages of corticogenesis.
在哺乳动物皮质发生过程中,一系列短暂的细胞层形成了层状结构。由最早生成的神经元形成的前板,分离为边缘区和板下层。为了系统筛选参与板下发育和功能的基因,我们筛选了使用细菌人工染色体方法(基因表达神经系统图谱计划)生成的转基因小鼠品系,以鉴定在 destined for the subplate(此处原文有误,可能是“destined for the subplate layer”,即注定进入板下层)的前板神经元中表达增强型绿色荧光蛋白(EGFP)报告基因的小鼠转基因品系。从EGFP阳性神经元纯化的RNA的基因表达谱鉴定出200多个在未来板下神经元中表达丰富的基因。板下富集基因的主要类别包括参与转录过程、皮质发育、细胞和轴突运动、蛋白质运输和类固醇激素信号传导的基因。此外,我们鉴定出10个与大脑和小脑皮质退行性疾病相关的基因。基于Cre重组酶的表达磷酸二酯酶1c(Pde1c)的细胞命运图谱显示,在脑室区以及板下层中有β-半乳糖苷酶阳性细胞,这表明板下神经元和皮质投射神经元可能源自共同的祖细胞。因此,这些实验揭示了从发育最早阶段就可鉴定板下神经元的遗传标记,以及在皮质发生早期板下神经元中表达丰富的基因。