中文摘要：

目的探讨音猬因子信号通路成员与胰岛素增强子结合蛋白在呼吸系统的早期表达与其发育的联系。方法胚龄9.0~13d小鼠胚胎呼吸系统各年龄段不小于3个,连续石蜡切片,用抗音猬因子（Shh）、抗patched1（Ptcl）、抗smoothened（Smo）、抗胰岛素增强子结合蛋白（ISL1）和抗α-平滑肌肌动蛋白（α-SMA）抗体进行免疫组织化学染色。结果胚龄10d,Shh表达在前肠内胚层腹侧壁。胚龄11~12d,Ptc1表达在气管、支气管和肺内分支上皮。胚龄13d,Ptc1只表达在肺内分支上皮。胚龄9d,ISL1表达在前肠内胚层腹侧壁。胚龄10~12d,ISL1表达在前肠（气管）腹侧壁和支气管侧壁上皮及邻近的间充质内。胚龄13d,ISL1表达减弱,始终未见在肺内有阳性表达。胎龄12~13d,与气管后壁、支气管内侧壁上皮Ptc1表达减弱处相邻的间充质出现α-SMA阳性平滑肌细胞,其与对侧间充质ISL1阳性细胞的分布呈背-腹侧或内-外侧模式。气管腹侧及肺芽外侧间充质中可见ISL1与Smo共表达细胞。结论 ISL1在气管及肺芽的发育中可能与Shh信号系统协同发挥作用。

英文摘要：

Objective To explore the relationship of the early morphogenesis of respiratory system with the expression of islet-1（ ISL1） and sonic hedgehog（ Shh）-patched 1（ Ptc1）-smoothened（ Smo） pathway. Methods Serial sections of three mouse embryos each day from embryonic day（ ED） 9. 0 to ED 13 were stained immunohistochemically with antibodies against Shh,Ptcl,Smo,ISL1 and α-smooth muscle actin（ α-SMA）. Results At ED10,Shh was detected in the endodermal epithelium ventral to the foregut. From ED11 to ED12,Ptc1 was present in epithelial cells of both the trachea,bronchies and branching of lung buds. At ED13,Ptc1 expression was restricted to epithelial cells of airway in lung. At ED9,ISL1 staining of epithelial cells was observed in endoderm ventral to the foregut. From ED11 to ED12,ISL1 staining was observed in epithelial and mesenchyme cells surrounding ventral to the trachea and lateral to the bronchies,where co-localization of ISL1 with Smo was detected. At ED13,ISL1 staining was reduced,while little present in the distal airway of the developing lung. From ED12 to ED13,α-SMA positive smooth muscle cells were detected in mesenchyme adjacent closely to the dorsal wall of trachea and between bronchies where Ptc1 staining was negative in the epithelial. The distribution pattern of ISL1 positive cells and α-SMA positive cells in mesenchyme around trachea and bronchies was in dorsal-ventral or inner-lateral direction. Conclusion ISL1 may play an important role in normal morphogenesis of the trachea and lung buds in coordination with members of Shh-Ptc1-Smo pathway.