Shaping the Face: Genetic Interactions in Zebrafish Jaw Development

Development of the jaw skeleton can be divided into three stages: (1) migration of neural crest cells, precursors of jaw skeletal cells, (2) aggregation of neural crest cells into pharyngeal arches, and (3) differentiation of pharyngeal arch cells into skeletal cells. Signaling between cells is instrumental in all three stages. One signal, Endothelin-1 (edn1), is known to be required for lower jaw development in zebrafish. Work in mice has shown that the signaling molecule Fibroblast growth factor-8 (fgf8) is required for proper edn1 expression, motivating the following hypothesis: edn1 and fgf8a genetically interact in zebrafish jaw development. / We tested this hypothesis by generating fish that carry mutations in both edn1 and fgf8a. These fish are missing cartilage cells from their upper jaw, a phenotype not present in either single mutant. To investigate the cause of this phenotype we examined cells of the pharyngeal arches. We found that the first arch, which is the precursor to the lower and upper jaw, to be dysmorphic. We then examined neural crest cell migration. While migration appeared normal, neural crest cells failed to aggregate into the intermediate region of the first arch in double mutant fish, placing the manifestation of the double mutant phenotype in stage two of jaw skeleton development. Our findings suggest a novel genetic interaction or synergy between edn1 and fgf8a in which they function to promote aggregation of neural crest cells into the intermediate region of the first pharyngeal arch.