Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N
Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto City, Kyoto, 606-8501, Japan.
Biochem Biophys Res Commun. 2000 Nov 2;277(3):643-9. doi: 10.1006/bbrc.2000.3721.
FGF receptor 2 isoform IIIb (FGFR2b), originally discovered as a receptor for FGF7, is known to be an important receptor in vertebrate morphogenesis, because FGFR2b null mice exhibit agenesis or dysgenesis of various organs, which undergo budding and branching morphogenesis. Since FGF7 null mice do not exhibit marked defects in organogenesis, it has been considered that other FGF(s) than FGF7 might function as a major ligand for FGFR2b during organogenesis. One of the candidate ligands is FGF10, because FGF10 binds to FGFR2b with high affinity and the formation of the limb and lung is arrested in FGF10 null mice as found in FGFR2b-deficient mice. Previous analyses of FGF10 null mice revealed that FGF10 is required for limb and lung development. To elucidate the role of FGF10 in wide-range organogenesis, we further analyzed the phenotypes of the FGF10 knockout mice. We found diverse phenotypes closely related to those for FGFR2b-deficient mice, which includes the absence of thyroid, pituitary, and salivary glands, while minor defects were observed in the formation of teeth, kidneys, hair follicles, and digestive organs. These results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development.
成纤维细胞生长因子受体2亚型IIIb(FGFR2b)最初作为FGF7的受体被发现,已知是脊椎动物形态发生中的重要受体,因为FGFR2b基因敲除小鼠表现出各种器官的发育不全或发育异常,这些器官会经历出芽和分支形态发生。由于FGF7基因敲除小鼠在器官发生过程中未表现出明显缺陷,因此人们认为在器官发生过程中,除FGF7外的其他成纤维细胞生长因子(FGF)可能作为FGFR2b的主要配体发挥作用。候选配体之一是FGF10,因为FGF10与FGFR2b具有高亲和力结合,并且如在FGFR2b缺陷小鼠中所发现的那样,FGF10基因敲除小鼠的四肢和肺部形成受阻。先前对FGF10基因敲除小鼠的分析表明,FGF10是四肢和肺部发育所必需的。为了阐明FGF10在广泛器官发生中的作用,我们进一步分析了FGF10基因敲除小鼠的表型。我们发现了与FGFR2b缺陷小鼠密切相关的多种表型,包括甲状腺、垂体和唾液腺缺失,而在牙齿、肾脏、毛囊和消化器官的形成中观察到轻微缺陷。这些结果表明,FGF10在小鼠多器官发育中作为FGFR2b的主要配体发挥作用。