Taste sensory capability is mediated by aggregates of receptor cells, called taste buds, which reside within the oral and pharyngeal cavities. The majority of taste buds in mammals reside on the tongue in epithelial-mesenchymal specializations termed gustatory papillae. In the rodent tongue, the smaller fungiform papillae, each of which possesses a single taste bud, are found in a distributed array on the anterior tongue. By contrast, the larger bilateral foliate papillae and a single midline circumvallate papilla (CVP) each house hundreds of buds and reside on the posterior tongue (). Recently, there has been increasing recognition that anterior fungiform taste buds differ from those of the posterior CVP in terms of both gene expression and taste function 
Deletion of Spry2 leads to a duplication of the CVP in the posterior tongue.
In recent years, significant progress has been made in defining the molecular regulation of fungiform development. Fungiform papillae initially form as placodes that subsequently undergo epithelial morphogenesis and acquire a mesenchymal core 
in a process that is similar to morphogenesis of other vertebrate epithelial specializations, such as hair, teeth, and mammary glands 
. The development of these other organs requires signaling between epithelium and mesenchyme, suggesting that such epithelial-mesenchymal interactions are also involved in patterning and morphogenesis of taste placodes. However, expression of all of the key signaling factors implicated in taste placode development – including Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF), and WNTs – is restricted to the epithelium 
. Thus, to date, no inductive, mesenchyme-derived factor involved in taste development has been identified.
Despite its importance in taste function and its status as the largest of the taste papillae, very little is known about the genes involved in the development of the CVP. Like fungiform placodes, the CVP forms as an initial epithelial thickening that undergoes complex morphogenesis to form a large papilla. However, it appears that genes known to regulate fungiform development do not function similarly in development of the CVP. For example, inhibition of SHH results in more and larger fungiform placodes, but has no effect on the CVP 
. In addition, BMP7 and its antagonist follistatin have significant functions in fungiform development, but the CVP appears unaffected by inactivation of either gene 
. These differences may be ascribed to the distinct embryonic origins of the anterior tongue, which is thought to be derived from ectoderm, whereas the posterior tongue likely has endodermal origins 
Expression of several Fibroblast Growth Factors (FGFs) and their receptors has previously been detected in the developing tongue 
. Therefore, we hypothesized that Sprouty (Spry) genes, which antagonize several receptor-tyrosine kinase (RTK) signaling pathways including those triggered by FGFs 
, may play a role in the development of taste papillae. Originally, spry
was identified as a regulator of tracheal branching in Drosophila 
, and it was later found that three of the four mouse Sprouty genes (Spry1
, and Spry4
) are expressed during embryonic development 
Here, we used mouse genetic models to show that FGF signaling is required for CVP formation. We found that Spry1 and Spry2 antagonize signaling by FGF10 to restrict the size of the progenitor field of the circumvallate (CV) placode, such that loss of Sprouty function results in a dramatic expansion of the CV placode as it first forms. In adult Spry2 mutants, a striking and complete duplication of the CVP emerges, whereas embryos lacking both Spry1 and Spry2 have multiple CVPs. Our findings thus represent the first example of molecular genetic regulation of taste organs in the posterior tongue. We found that Fgf10, which is expressed exclusively in the mesenchyme underlying the CV placode, is required for formation of the CVP, and thus we provide the first example of an inductive, mesenchymal signal involved in specifying the epithelial domain of a developing taste papilla. Further, while FGF10 signaling drives CVP development and Spry1 and Spry2 repress this process, fungiform taste papillae are oppositely affected by the loss of these genes: Fgf10−/− tongues appear to possess more and larger fungiform papillae, and the loss of Sprouty genes results in fewer fungiform papillae. Thus, these results demonstrate that molecular mechanisms regulating development of anterior and posterior taste organs differ considerably. Finally, we postulate that the role of FGF signaling in defining the size of the CV progenitor field in mice may underlie the large variation in CVP number across mammalian taxa, and that changes in FGF signaling during evolution may have caused expansion of the initial progenitor field to allow formation of multiple CVPs in some species.