Spencer-Dene Bradley, Sala Frederic G, Bellusci Saverio, Gschmeissner Stephen, Stamp Gordon, Dickson Clive
Experimental Pathology Laboratory, Cancer Research UK, London Research Institute, London, England.
Gastroenterology. 2006 Apr;130(4):1233-44. doi: 10.1053/j.gastro.2006.02.018.
BACKGROUND & AIMS: Fibroblast growth factors (Fgfs) and their receptors (Fgfrs) are important intercellular signaling molecules that are essential to mammalian embryonic development. The signaling pathways between endoderm-derived gastric epithelium and the surrounding mesenchyme are largely unknown; however, the developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its main ligand, Fgf10, suggest that they may be strong candidates. Mice lacking either component (Fgfr2b-/- or Fgf10-/-) were examined to determine the role of Fgfr2b-mediated signaling during gastric organogenesis.
Stomachs from embryonic day 13.5-18.5 Fgfr2b-/-, Fgf10-/-, and wild-type littermates were collected and analyzed by conventional histology, immunohistochemistry, in situ hybridization, and electron microscopy.
Fgfr2b-/- and Fgf10-/- fetuses had stomachs smaller than wild-type, consisting of relatively proportionate forestomach but disproportionately reduced glandular stomach, the mucosa of which has low cytoarchitectural complexity with a spiral arrangement of large mucosal folds. During mid to late fetal stages (embryonic day 15.5-18.5), epithelial differentiation to mucous and chief cell lineages was rudimentary, with no expression of several early cytodifferentiation markers including GATA4, GATA6, and H+/K+-adenosine triphosphatase and abnormal expression of members of the hedgehog family of signaling molecules.
Fgfr2b and Fgf10 are part of a signaling network with Sonic hedgehog and Indian hedgehog that are essential to anterior-posterior and radial patterning in gastric development.
成纤维细胞生长因子（Fgfs）及其受体（Fgfrs）是重要的细胞间信号分子，对哺乳动物胚胎发育至关重要。内胚层来源的胃上皮与周围间充质之间的信号通路在很大程度上尚不清楚；然而，Fgfr2的IIIb亚型（Fgfr2b）及其主要配体Fgf10的发育表达谱表明它们可能是有力的候选者。对缺乏任一成分（Fgfr2b-/-或Fgf10-/-）的小鼠进行研究，以确定Fgfr2b介导的信号在胃器官发生过程中的作用。
收集胚胎第13.5 - 18.5天的Fgfr2b-/-、Fgf10-/-和野生型同窝小鼠的胃，通过传统组织学、免疫组织化学、原位杂交和电子显微镜进行分析。
Fgfr2b-/-和Fgf10-/-胎儿的胃比野生型小，前胃相对比例正常，但腺胃不成比例地缩小，其黏膜细胞结构复杂性低，有大的黏膜皱襞呈螺旋状排列。在胎儿中晚期（胚胎第15.5 - 18.5天），上皮向黏液细胞和主细胞谱系的分化基本未发育，包括GATA4、GATA6和H+/K+-三磷酸腺苷酶在内的几种早期细胞分化标志物无表达，且信号分子刺猬家族成员表达异常。
Fgfr2b和Fgf10是与音猬因子和印度刺猬因子组成的信号网络的一部分，对胃发育中的前后和径向模式形成至关重要。
