Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo.
Bottom Line: 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.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.
Affiliation: Department of Craniofacial Development, King's College London, Floor 27, Guy's Tower, London, SE1 9RT, UK.Show MeSH
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Mentions: Sprouty proteins regulate signalling via the MAPK pathway, which is activated downstream of a number of receptor tyrosine kinases, including FGF receptors and RET (Basson et al., 2005, 2006; Mason et al., 2006; Rozen et al., 2009; Shim et al., 2005). To determine to what extent the observed defects are due to hyperactive FGF signalling, we attempted to rescue the Spry1−/−;Spry2−/− mutant phenotype by reducing the Fgf8 gene dosage as previously described for Spry2 mutant phenotypes (Shim et al., 2005). The epibranchial cranial nerves in Spry1−/−;Spry2−/−;Fgf8+/− embryos (Figs. 6C,D) exhibited similar phenotypes to those observed in Spry1−/−;Spry2−/− (Fig. 6B). However, whereas the incidence of phenotypes found in the developing facial and vagus cranial nerves were similar between Spry1−/−;Spry2−/− and Spry1−/−;Spry2−/−;Fgf8+/− embryos, the density of glossopharyngeal nerve fibres was rescued in some Spry1−/−;Spry2−/−;Fgf8+/− embryos (Figs. 6C,D, Table 1). To explore the reason for this partial phenotypic rescue further, we compared the forming epibranchial placodes in Spry1−/−;Spry2−/− and Spry1−/−;Spry2−/−;Fgf8+/− embryos. Both the enlarged geniculate and absent petrosal and nodose phenotypes were partially rescued by a reduction in the Fgf8 gene dosage at E9.5 (n = 4; Figs. 6E–G). This observation suggests that increased signalling downstream of FGF8 may be responsible for these early defects in placodal development.
Affiliation: Department of Craniofacial Development, King's College London, Floor 27, Guy's Tower, London, SE1 9RT, UK.