Thisse B, Thisse C, Weston J A
Institut de Génétique et de Biologies Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
Dev Dyn. 1995 Jul;203(3):377-91. doi: 10.1002/aja.1002030309.
We have identified a novel FGF receptor, Z-FGFR4, in zebrafish embryos. Z-FGFR4 is closely related to both chicken FREK (Marcelle et al. [1994] Development 120:683-694) and the Pleurodeles cDNA clone Pw-FGFR4 (also named PFR4). The Z-FGFR4 cDNA clones contain consensus sequences for two groups of two Ig-like domains, separated by eight acidic residues referred to as the "acid box." Z-FGFR4, therefore, is the first FGFR molecule yet described in vertebrates that contains four Ig domains in its amino-terminal region. Whole-mount in situ hybridization of staged zebrafish embryos, using probes prepared from a variety of domains of the Z-FGFR4 cDNA, reveal complex temporal and spatial expression patterns. Expression of Z-FGFR4 mRNA is first detected in embryos prior to gastrulation and then appears in prechordal plate mesendoderm. At this time, Z-FGFR mRNA is expressed in the epiblast in two distinct stripes which ultimately contribute to the brain. Eventually Z-FGFR4 transcripts are observed in forebrain, anterior hindbrain (rhombomeres 1, 3), and caudal hindbrain (rhombomere 7), as well as in the dorsal-most portion of the rostral spinal cord. Expression in axial mesendoderm appears transiently in notochord and segmental plate mesoderm. Eventually, Z-FGFR4 mRNA becomes restricted to the posterior somites and is absent in differentiated notochord. These detailed expression studies provide the basis for understanding FGFR function through an analysis, currently in progress, of the developmental consequences of Z-FGFR4 misexpression.
我们在斑马鱼胚胎中鉴定出一种新型成纤维细胞生长因子受体(FGF受体),即Z-FGFR4。Z-FGFR4与鸡的FREK(Marcelle等人,[1994]《发育》120:683 - 694)以及蝾螈cDNA克隆Pw-FGFR4(也称为PFR4)密切相关。Z-FGFR4 cDNA克隆包含两组两个免疫球蛋白样结构域的共有序列,中间由八个酸性残基隔开,这八个酸性残基被称为“酸性框”。因此,Z-FGFR4是脊椎动物中首个在其氨基末端区域含有四个免疫球蛋白结构域的FGFR分子。使用从Z-FGFR4 cDNA的多个结构域制备的探针,对不同发育阶段的斑马鱼胚胎进行整体原位杂交,揭示了复杂的时空表达模式。Z-FGFR4 mRNA的表达首先在原肠胚形成之前的胚胎中被检测到,然后出现在脊索前板中内胚层。此时,Z-FGFR mRNA在胚盘上以两条不同的条纹形式表达,最终形成大脑。最终,在端脑、前脑后部(菱脑节1、3)、后脑尾部(菱脑节7)以及脊髓最前端的背侧部分观察到Z-FGFR4转录本。在轴中内胚层的表达短暂出现在脊索和体节板中胚层。最终,Z-FGFR4 mRNA局限于后部体节,在分化的脊索中不存在。这些详细的表达研究为通过目前正在进行的对Z-FGFR4异常表达的发育后果的分析来理解FGFR功能提供了基础。