小鼠胚胎心流出道发育中胰岛因子1的表达及意义

The expression and significance of ISL-1 in the development of outflow tract of mouse embryonic heart

目的观察胰岛因子1(Islet-1,ISL-1)在小鼠胚胎心流出道发育中的表达,探讨ISL-1阳性细胞在第二生心区的时空分布特点及其在心流出道发育中的作用。方法 15只胚龄8.5d^12d小鼠胚胎心连续石蜡切片,选用抗α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、抗心肌肌球蛋白重链(myosinheavy chain,MHC)和抗ISL-1抗体,进行免疫组织化学染色。结果胚龄8.5d^10d,ISL-1阳性细胞相继出现在流出道远端、心包腔背侧脏壁和体壁中胚层、原始咽腹外侧间充质及第2对鳃弓核心间充质,并逐渐分化为心肌细胞添加到流出道远端;胚龄11d,咽腹侧ISL-1阳性细胞形成独特的锥形结构,形成主肺动脉隔的雏形;胚龄12d,ISL-1阳性锥形结构与流出道远端心内膜垫融合形成主肺动脉隔,此时ISL-1阳性细胞开始分化为平滑肌细胞,参与心包腔内升主动脉、肺动脉干和主肺动脉隔的发育。结论第二生心区涵盖了原始咽腹外侧间充质、心包腔背侧壁中胚层及鳃弓核心间充质等多个区域,其中的ISL-1阳性细胞具有多向分化潜能,在心发育的不同阶段可以分化为不同类型的细胞,参与流出道的正常发育。

Objective To observe the expression of Islet-1（ISL-1） during the development of outflow tract（OFT） of mouse embryonic heart and to explore the spatial-temporal distribution pattern of ISL-1-positive cells in the second heart field（SHF） as well as the role of ISL-1 in the development of OFT of mouse embryonic heart.Methods Serial sections of fifteen mouse embryonic hearts from embryonic day（ED） 8.5 to ED 12 were stained immunohistochemically with antibodies against α-smooth muscle actin（α-SMA）,myosin heavy chain（MHC） and ISL-1.Results From ED8.5 to ED10,ISL-1-positive cells were sequentially detected in the distal pole of OFT,the splanchnic mesoderm dorsal to pericardial cavity,the mesenchyme ventral-lateral to the primary pharynx,and the core mesenchyme of the second branchial arches,gradually differentiating into cardiomyocytes and adding to the distal pole of OFT;At ED 11,ISL-1-positive cells ventral to pharynx grew into a unique cone-shaped structure to form the rudiment of aorto-pulmonary septum（AP septum）;At ED12,the cone-shaped structure constituted of ISL-1-positive cells fused with the endocardial cushion at the distal pole of OFT to form the AP septum while the ISL-1-positive cells differentiated into smooth muscle in the walls of the intrapericardial aorta and pulmonary trunk as well as the AP septum.Conclusion SHF covered various areas including the mesenchyme ventral-lateral to the primary pharynx,the mesoderm dorsal to the pericardial cavity as well as the core mesenchyme of the second branchial arches.ISL-1-positive cells with multiple differentiation potency could differentiate into several cell types during different stages of cardiac development,contributing to the normal development of OFT.