Gryzik Tanja, Müller H-Arno J
Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Curr Biol. 2004 Apr 20;14(8):659-67. doi: 10.1016/j.cub.2004.03.058.
Mesoderm migration in the Drosophila gastrula depends on the fibroblast growth factor (FGF) receptor Heartless (Htl). During gastrulation Htl is required for adhesive interactions of the mesoderm with the ectoderm and for the generation of protrusive activity of the mesoderm cells during migration. After gastrulation Htl is essential for the differentiation of dorsal mesodermal derivatives. It is not known how Htl is activated, because its ligand has not yet been identified.
We performed a genome-wide genetic screen for early zygotic genes and identified seven genomic regions that are required for normal migration of the mesoderm cells during gastrulation. One of these genomic intervals produces upon its deletion a phenocopy of the htl cell migration phenotype. Here we present the genetic and molecular mapping of this genomic region. We identified two genes, FGF8-like1 and FGF8-like2, that encode novel FGF homologs and were only partially annotated in the Drosophila genome. We show that FGF8-like1 and FGF8-like2 are expressed in the neuroectoderm during gastrulation and present evidence that both act in concert to direct cell shape changes during mesodermal cell migration and are required for the activation of the Htl signaling cascade during gastrulation.
We conclude that FGF8-like1 and FGF8-like2 encode two novel Drosophila FGF homologs, which are required for mesodermal cell migration during gastrulation. Our results suggest that FGF8-like1 and FGF8-like2 represent ligands of the Htl FGF receptor.
果蝇原肠胚中胚层迁移依赖于成纤维细胞生长因子(FGF)受体“无心脏”(Htl)。在原肠胚形成过程中,Htl对于中胚层与外胚层的黏附相互作用以及中胚层细胞迁移过程中突出活性的产生是必需的。原肠胚形成后,Htl对于背侧中胚层衍生物的分化至关重要。目前尚不清楚Htl是如何被激活的,因为其配体尚未被鉴定出来。
我们对早期合子基因进行了全基因组遗传筛选,确定了七个基因组区域,这些区域是原肠胚形成过程中中胚层细胞正常迁移所必需的。其中一个基因组区间在缺失后产生了与htl细胞迁移表型相似的拟表型。在此,我们展示了该基因组区域的遗传和分子定位。我们鉴定出两个基因,FGF8-like1和FGF8-like2,它们编码新的FGF同源物,并且在果蝇基因组中仅有部分注释。我们表明,FGF8-like1和FGF8-like2在原肠胚形成期间在神经外胚层中表达,并提供证据表明二者共同作用以指导中胚层细胞迁移过程中的细胞形状变化,并且是原肠胚形成期间Htl信号级联激活所必需的。
我们得出结论,FGF8-like1和FGF8-like2编码两种新的果蝇FGF同源物,它们是原肠胚形成期间中胚层细胞迁移所必需的。我们的结果表明,FGF8-like1和FGF8-like2代表Htl FGF受体的配体。