Shin Masahiro, Noji Sumihare, Neubüser Annette, Yasugi Sadao
Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minamiohsawa, Hachioji, Tokyo 192-0397, Japan.
Dev Biol. 2006 Jun 1;294(1):11-23. doi: 10.1016/j.ydbio.2005.12.019. Epub 2006 Apr 17.
The development of digestive organs in vertebrates involves active epithelial-mesenchymal interactions. In the chicken proventriculus (glandular stomach), the morphogenesis and cytodifferentiation of the epithelium are controlled by the inductive signaling factors that are secreted from the underlying mesenchyme. Previous studies have shown that Fgf10 is expressed in the developing chicken proventricular mesenchyme, whereas its receptors are present in the epithelium. In our present study, we show that FGF10 is an early mesenchymal signal that is critically associated with the developmental processes in the proventricular epithelium. Furthermore, virus-mediated Fgf10 overexpression in ovo results in a hypermorphic epithelial structure and an increase in epithelial cell number. In contrast, the overexpression of a secreted FGFR2b (sFGFR2b), an FGF10 antagonist, blocks cell proliferation and gland formation in the proventricular epithelium in ovo. This downregulation of proliferative activity was subsequently found to retard gland formation and also to delay differentiation of the epithelium. These results demonstrate that FGF10 signaling, mediated by FGFR1b and/or FGFR2b, is required for proliferation and gland formation in the epithelium in the developing chick embryo.
脊椎动物消化器官的发育涉及活跃的上皮-间充质相互作用。在鸡的前胃(腺胃)中,上皮的形态发生和细胞分化受来自其下方间充质分泌的诱导信号因子的控制。先前的研究表明,Fgf10在发育中的鸡前胃间充质中表达,而其受体存在于上皮中。在我们目前的研究中,我们表明FGF10是一种早期间充质信号,与前胃上皮的发育过程密切相关。此外,病毒介导的Fgf10在鸡胚内过表达导致上皮结构过度发育和上皮细胞数量增加。相反,FGF10拮抗剂分泌型FGFR2b(sFGFR2b)的过表达会阻断鸡胚内前胃上皮中的细胞增殖和腺体形成。随后发现这种增殖活性的下调会阻碍腺体形成,并延迟上皮的分化。这些结果表明,由FGFR1b和/或FGFR2b介导的FGF10信号传导是发育中的鸡胚上皮细胞增殖和腺体形成所必需的。