Sprouty1 and Sprouty2 limit both the size of the otic placode and hindbrain Wnt8a by antagonizing FGF signaling

Multiple signaling molecules, including Fibroblast Growth Factor (FGF) and Wnt, induce two patches of ectoderm on either side of the hindbrain to form the progenitor cell population for the inner ear, or otic placode. Here we report that in Spry1, Spry2 compound mutant embryos (Spry1−/−; Spry2−/− embryos), the otic placode is increased in size. We demonstrate that the otic placode is larger due to the recruitment of cells, normally destined to become cranial epidermis, into the otic domain. The enlargement of the otic placode observed in Spry1−/−; Spry2−/− embryos is preceded by an expansion of a Wnt8a expression domain in the adjacent hindbrain. We demonstrate that both the enlargement of the otic placode and the expansion of the Wnt8a expression domain can be rescued in Spry1−/−; Spry2−/− embryos by reducing the gene dosage of Fgf10. Our results define a FGF-responsive window during which cells can be continually recruited into the otic domain and uncover SPRY regulation of the size of a putative Wnt inductive center. ► The otic placode is enlarged in Sprouty1, Sprouty2 compound mutants. ► This enlargement is due to the recruitment of cells into the otic domain. ► Sprouty1, 2 transcripts are present in tissues responsive to FGF signals. ► Wnt8a expression in the hindbrain is expanded in Sprouty1, 2 compound mutants. ► Sprouty1, 2 antagonize FGF10 induction of the otic placode and Wnt8a expression.