Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo

Fibroblast growth factor (FGF) signalling has important roles in the development of the embryonic pharyngeal (branchial) arches, but its effects on innervation of the arches and associated structures have not been studied extensively. We investigated the consequences of deleting two receptor tyrosine kinase (RTK) antagonists of the Sprouty (Spry) gene family on the early development of the branchial nerves. The morphology of the facial, glossopharyngeal and vagus nerves are abnormal in Spry1−/−;Spry2−/− embryos. We identify specific defects in the epibranchial placodes and neural crest, which contribute sensory neurons and glia to these nerves. A dissection of the tissue-specific roles of these genes in branchial nerve development shows that Sprouty gene deletion in the pharyngeal epithelia can affect both placode formation and neural crest fate. However, epithelial-specific gene deletion only results in defects in the facial nerve and not the glossopharyngeal and vagus nerves, suggesting that the facial nerve is most sensitive to perturbations in RTK signalling. Reducing the Fgf8 gene dosage only partially rescued defects in the glossopharyngeal nerve and was not sufficient to rescue facial nerve defects, suggesting that FGF8 is functionally redundant with other RTK ligands during facial nerve development.
Highlights ► Sprouty gene deletion in mouse embryos cause multiple defects in epibranchial ganglia. ► Both epibranchial placodes and neural crest cells are affected. ► Sprouty gene function is required in the pharyngeal ectoderm and endoderm. ► Hyperactive FGF8 signalling is in part responsible for these defects.