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Abstract：
Fibroblast growth factor (Fgf) signaling regulates many processes during development. In most cases, one tissue layer secretes an Fgf ligand that binds and activates an Fgf receptor (Fgfr) expressed by a neighboring tissue. Although studies have identified the roles of specific Fgf ligands during development, less is known about the requirements for the receptors. We have generated null mutations in each of the five fgfr genes in zebrafish. Considering the diverse requirements for Fgf signaling throughout development, and that null mutations in the mouse Fgfr1 and Fgfr2 genes are embryonic lethal, it was surprising that all zebrafish homozygous mutants are viable and fertile, with no discernable embryonic defect. Instead, we find that multiple receptors are involved in coordinating most Fgf-dependent developmental processes. For example, mutations in the ligand fgf8a cause loss of the midbrain-hindbrain boundary, whereas, in the fgfr mutants, this phenotype is seen only in embryos that are triple mutant for fgfr1a;fgfr1b;fgfr2, but not in any single or double mutant combinations. We show that this apparent fgfr redundancy is also seen during the development of several other tissues, including posterior mesoderm, pectoral fins, viscerocranium, and neurocranium. These data are an essential step toward defining the specific Fgfrs that function with particular Fgf ligands to regulate important developmental processes in zebrafish.
摘要：
成纤维细胞生长因子（Fgf）信号调节发育过程中的许多过程。在大多数情况下,一个组织层分泌结合并激活由邻近组织表达的Fgf受体(Fgfr)的Fgf配体。尽管研究已经确定了特定Fgf配体在发育过程中的作用，对受体的要求知之甚少。我们已经在斑马鱼的五个fgfr基因中产生了无效突变。考虑到整个开发过程中对Fgf信令的不同要求，小鼠Fgfr1和Fgfr2基因中的无效突变是胚胎致死性的，令人惊讶的是，所有斑马鱼纯合突变体都是可行的和可育的，没有明显的胚胎缺陷.相反，我们发现多种受体参与协调大多数Fgf依赖性发育过程。例如,配体fgf8a的突变导致中脑-后脑边界的丧失，然而,在fgfr突变体中，这种表型只见于fgfr1a、fgfr1b、fgfr2三重突变的胚胎，但不见于任何单或双突变组合。我们表明，在其他几个组织的发育过程中也可以看到这种明显的fgfr冗余，包括后中胚层,胸鳍,内脏ocranium,和神经头颅。这些数据是定义与特定Fgf配体起作用以调节斑马鱼重要发育过程的特定Fgfrs的重要步骤。
