FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size

Abstract

The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP). Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry) genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK) signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1−/−;Spry2−/− embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway.

Coevolutionary patterning of teeth and taste buds

“…S6 and S7, and Table S2). FGF signal plays known roles in the patterning of teeth and taste buds in the mouse (21,22) and in the zebrafish pharynx (23,24), but its function in the oral jaws of teleost fishes is less clear. Here, we observed fgf10 in condensed dental mesenchyme, fgf7 in the forming velum lingual to teeth/taste buds, and no activity of fgf8 in the oral organ field (see also ref.…”

Progress and renewal in gustation: new insights into taste bud development

“…In Fgf10 knockouts, the CVP does not form, while CVP mispatterning in Spry2 −/− embryos is partially rescued in Fgf10 +/− hemizygotes. Interestingly, Spry2 function appears to be distinct for anterior versus posterior taste papillae, as the number of FFP is reduced, rather than expanded as is the case for the CVP, in Spry2 −/− tongues (Petersen et al, 2011).…”

“…1). The number and pattern of taste papillae types vary in mammals (Petersen et al, 2011;Reiner et al, 2008;Witt and Miller, 1992), but rodents possess a single midline CVP, bilaterally located FolP, each containing hundreds of taste buds, and anteriorly arrayed FFP, each housing one taste bud (Fig. 1).…”

“…The Sprouty genes Spry1-4 encode negative intracellular regulators of receptor tyrosine kinases, including FGF receptors. Loss of Spry2 causes duplication of CVP; when Spry1 and 2 are deleted, three or more CVP form (Petersen et al, 2011). Epithelial Spry2 primarily regulates the inductive role of mesenchymal Fgf10.…”

“…In fact, Sox2 is likely to have broad roles in the lingual epithelium, as both taste placodes and the non-taste epithelium express Sox2, albeit at high and low levels, respectively (Nakayama et al, 2015;Okubo et al, 2006). Nonetheless, with respect to taste placodes, Sox2 is positively regulated by Wnt/ β-catenin and Fgf10/Spry2 signaling (Okubo et al, 2006;Petersen et al, 2011). Whether Sox2 is regulated by Shh during taste bud development is unknown, although Sox2 appears to function downstream of Shh during adult taste cell renewal (see below) (Castillo et al, 2014).…”