Constitutive Activation of HH-GLI Signaling in the Metanephric Mesenchyme causes Ureteropelvic Junction Obstruction during Mammalian Embryogenesis

This study explores the underlying pathogenic mechanisms of congenital intrinsic obstruction of the ureteropelvic junction. A hedgehog-dependent mechanism underlying mammalin intrinsic ureteropelvic obstruction is defined. Tissue was microdissected from the kidney-ureter junction at E13.5, one day after the onset of Ptc2-lacZ expression, from PTC-/-MM mice; 2 PTC2+ and 2 PTC2- cell populations were isolated using antibodies specific for PTC2 and FACS sorting.本研究探讨先天性肾盂输尿管连接部梗阻（congenital intrinsic obstruction of the ureteropelvic junction）的潜在致病机制。本研究明确了哺乳动物先天性肾盂输尿管梗阻背后依赖于刺猬信号通路（Hedgehog）的分子机制。研究人员于胚胎第13.5天（E13.5），即Ptc2-lacZ报告基因表达启动1天后，从PTC基因敲除MM（PTC-/-MM）小鼠的肾-输尿管连接部显微切割获取组织；随后利用靶向PTC2的特异性抗体及荧光激活细胞分选（Fluorescence-Activated Cell Sorting, FACS）技术，分离得到2个PTC2阳性（PTC2+）与2个PTC2阴性（PTC2-）细胞群。