A Potential Role of , , and in Pharyngeal Pouch Formation in Zebrafish.

In vertebrates, Fgf signaling is essential for the development of pharyngeal pouches, which controls facial skeletal development. Genetically, and are required for pouch formation in mice and zebrafish. However, loss-of-function phenotypes of and are milder than expected in mice and zebrafish, which suggests that an additional gene(s) would be involved in pouch formation. Here, we analyzed the expression, regulation, and function of three , , , and , during pouch development in zebrafish. We find that they are expressed in the distinct regions of pharyngeal endoderm in pouch formation, with and also being expressed in the adjacent mesoderm, in addition to previously reported endodermal and mesodermal expression. The endodermal expression of , , and and the mesodermal expression of and are positively regulated by Tbx1 but not by Fgf3, in pouch formation. Fgf8 is required to express the endodermal expression of and . Interestingly, however, single mutant, all double mutant combinations, and triple mutant for , , and do not show any defects in pouches and facial skeletons. Considering a high degree of genetic redundancy in the Fgf signaling components in craniofacial development in zebrafish, our result suggests that , , and have a potential role for pouch formation, with a redundancy with other gene(s).