Gene expression changes in limb buds of Nipbl-haploinsufficient mice

Multiple genes are dysregulated in hindlimb buds of Nipbl-deficient embryos. In all, more than 1000 limb bud genes were found to be significantly altered in expression by microarray analysis of E10.5 mouse hindlimb buds. Small changes in expression (mostly decreases) were observed for genes involved in FGF, BMP, and SHH pathways, as well as numerous genes involved in the Wnt/planar cell polarity signaling pathway. Genes involved in the Mediator complex, Cohesin function, and Hox gene expression and functions were also dysregulated in Nipbl deficient limb buds. Microarray analysis using RNA extracted from E10.5 hindlimb limb buds harvested from stage-matched Nipbl+/- (n=12) and wildtype (n=12)Nipbl缺陷型胚胎的后肢芽中存在多个基因表达失调现象。通过对E10.5小鼠后肢芽进行微阵列分析，共鉴定出超过1000个肢芽基因的表达水平发生显著改变。其中，参与成纤维细胞生长因子（FGF）、骨形态发生蛋白（BMP）以及音猬因子（SHH）信号通路的相关基因，以及大量参与Wnt/平面细胞极性信号通路（Wnt/planar cell polarity signaling pathway）的基因，其表达仅出现小幅变化（多数为表达下调）。参与中介体复合物（Mediator complex）、黏连蛋白（Cohesin）功能以及同源框基因（Hox gene）表达与调控功能的相关基因，在Nipbl缺陷型肢芽中同样出现表达失调。本研究采用从阶段匹配的Nipbl杂合子（n=12）与野生型（n=12）小鼠体内采集的E10.5后肢芽提取的RNA，开展微阵列分析。