Sharma Rahul, Beer Katharina, Iwanov Katharina, Schmöhl Felix, Beckmann Paula Indigo, Schröder Reinhard
University of Rostock, Biological Sciences, Department of Genetics, Albert-Einsteinstr. 3, 18059 Rostock, Germany.
University of Rostock, Biological Sciences, Department of Genetics, Albert-Einsteinstr. 3, 18059 Rostock, Germany.
Dev Biol. 2015 Jun 15;402(2):264-75. doi: 10.1016/j.ydbio.2015.04.001. Epub 2015 Apr 9.
The precise regulation of cell-cell communication by numerous signal-transduction pathways is fundamental for many different processes during embryonic development. One important signalling pathway is the evolutionary conserved fibroblast-growth-factor (FGF)-pathway that controls processes like cell migration, axis specification and mesoderm formation in vertebrate and invertebrate animals. In the model insect Drosophila, the FGF ligand / receptor combinations of FGF8 (Pyramus and Thisbe) / Heartless (Htl) and Branchless (Bnl) / Breathless (Btl) are required for the migration of mesodermal cells and for the formation of the tracheal network respectively with both the receptors functioning independently of each other. However, only a single fgf-receptor gene (Tc-fgfr) has been identified in the genome of the beetle Tribolium. We therefore asked whether both the ligands Fgf8 and Bnl could transduce their signal through a common FGF-receptor in Tribolium. Indeed, we found that the function of the single Tc-fgfr gene is essential for mesoderm differentiation as well as for the formation of the tracheal network during early development. Ligand specific RNAi for Tc-fgf8 and Tc-bnl resulted in two distinct non-overlapping phenotypes of impaired mesoderm differentiation and abnormal formation of the tracheal network in Tc-fgf8- and Tc-bnl(RNAi) embryos respectively. We further show that the single Tc-fgfr gene encodes at least two different receptor isoforms that are generated through alternative splicing. We in addition demonstrate through exon-specific RNAi their distinct tissue-specific functions. Finally, we discuss the structure of the fgf-receptor gene from an evolutionary perspective.
众多信号转导途径对细胞间通讯的精确调控是胚胎发育过程中许多不同进程的基础。一条重要的信号通路是进化上保守的成纤维细胞生长因子（FGF）通路，它在脊椎动物和无脊椎动物中控制着细胞迁移、轴的特化和中胚层形成等过程。在模式昆虫果蝇中，FGF8（Pyramus和Thisbe）/无心脏（Htl）以及无分支（Bnl）/呼吸急促（Btl）这两种FGF配体/受体组合分别是中胚层细胞迁移和气管网络形成所必需的，且这两种受体相互独立发挥作用。然而，在甲虫赤拟谷盗的基因组中仅鉴定出了一个fgf受体基因（Tc-fgfr）。因此，我们探究了Fgf8和Bnl这两种配体是否能通过赤拟谷盗中的一个共同FGF受体来转导它们的信号。事实上，我们发现单个Tc-fgfr基因的功能对于早期发育过程中的中胚层分化以及气管网络的形成至关重要。对Tc-fgf8和Tc-bnl进行配体特异性RNA干扰分别导致了Tc-fgf8-和Tc-bnl（RNAi）胚胎中中胚层分化受损和气管网络异常形成这两种不同且不重叠的表型。我们进一步表明，单个Tc-fgfr基因编码至少两种通过可变剪接产生的不同受体异构体。我们还通过外显子特异性RNA干扰证明了它们不同的组织特异性功能。最后，我们从进化的角度讨论了fgf受体基因的结构。
