Genetic analysis of fibroblast growth factor signaling during embryogenesis and early gonad development in zebrafish

The gonad is responsible for producing gametes, the specialized cells that organisms use to reproduce sexually. Therefore, proper gonad development is an essential component of species propagation. During early vertebrate gonadogenesis, primordial germ cells (the gamete lineage) and somatic gonad cell precursors (the supporting cell lineage) are specified independently and coalesce into a primordial gonad. This primitive gonad undergoes growth and morphogenesis before committing to a male or female fate. Once this decision is made, the bipotential gonad differentiates into a testis or ovary. Despite the importance of the gonad, little is known about the cellular communication events that drive early gonad development, in particular during the stages of coalescence, growth, and morphogenesis. Using mutational analysis in the vertebrate model organism, the zebrafish, I have discovered a required role for the Fibroblast growth factor (Fgf) signaling pathway during the stage of early gonad growth. I have shown that the ligand Fgf24 is produced by somatic gonad cells of the primordial gonad, and that its function is required for proliferation, differentiation, and morphogenesis of the somatic gonad. As a consequence of this defective somatic gonad, germ cells fail to develop, and most fgf24 mutants are sterile as adults. To further understand the downstream effects of Fgf24 signaling, I sought to identify its cognate receptor. I therefore generated null mutations in each of the five zebrafish Fgf receptor genes, with the prediction that disrupting the receptor that binds Fgf24 would result in a similar gonad defect to that of fgf24 mutants. However, I discovered that Fgf receptors function redundantly during gonad development. As a consequence, it is necessary to mutate three receptors simultaneously to observe gonadal defects. Interestingly, I observed similar receptor redundancy in development of the posterior mesoderm, pectoral fin limb bud, and brain, suggesting that this may be a common feature of the Fgf signaling pathway.