Clotman Frédéric, Libbrecht Louis, Killingsworth Murray C, Loo Christine C K, Roskams Tania, Lemaigre Frédéric P
Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
Liver Int. 2008 Mar;28(3):377-84. doi: 10.1111/j.1478-3231.2007.01617.x. Epub 2007 Nov 1.
BACKGROUND/AIMS: Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome.
Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy.
The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers.
Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.
背景/目的:梅克尔综合征是一种常染色体隐性疾病,其特征为肾囊肿、中枢神经系统异常、多指畸形以及导管板畸形(DPM)的组合,导管板畸形是由过多且异常的胎儿胆管结构组成的肝脏异常。在与梅克尔综合征相关的基因组位点中,最近鉴定出了四个基因的突变。这些基因编码与初级纤毛相关的蛋白质,可能参与细胞分化。本研究的目的是调查梅克尔综合征胎儿中初级纤毛的形成以及肝细胞的分化情况。
通过免疫荧光、免疫组织化学和电子显微镜对患有梅克尔综合征的人类胎儿肝脏切片进行分析。
在一些梅克尔综合征胎儿中,胆管细胞的初级纤毛缺失,但在其他胎儿中存在。此外,在梅克尔综合征胎儿的肝脏中观察到肝脏分化缺陷,共表达肝细胞和胆管标志物的杂交细胞的存在证明了这一点。
一些梅克尔综合征胎儿的肝脏中存在纤毛形成缺陷,并且大多数病例显示出与肝细胞异常分化相关的导管板畸形。由于在肝脏发育过程中分化先于纤毛形成,我们提出分化缺陷可能是梅克尔综合征胎儿肝脏中的初始缺陷。