FGF10 Is Required for Circumvallate Papilla Morphogenesis by Maintaining Lgr5 Activity

Abstract

Taste buds develop in different regions of the mammal oral cavity. Adult stem cells in various organs including the tongue papillae are marked by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homolog, Lgr6. Recent studies have reported that adult taste stem/progenitor cells in circumvallate papilla (CVP) on the posterior tongue are Lgr5-positive. In this study, we confirm the Lgr5 expression pattern during CVP development. A previous study reported that mesenchymal Fgf10 is necessary for maintaining epithelial Lgr5-positive stem/progenitor cells. To confirm the interaction between Lgr5-positive CVP epithelium and mesenchymal factor FGF10, reverse recombination (180-degree) was performed after tongue epithelium detachment. FGF10 protein-soaked bead implantation was performed after reverse recombination to rescue CVP development. Moreover, we reduced mesenchymal Fgf10 by BIO and SU5402 treatment which disrupted CVP morphogenesis. This study suggests that the crosstalk between epithelial Lgr5 and mesenchymal Fgf10 plays a pivotal role in CVP epithelium invagination during mouse tongue CVP development by maintaining Lgr5-positive stem/progenitor cells.

Action of Actomyosin Contraction With Shh Modulation Drive Epithelial Folding in the Circumvallate Papilla

“…Previously, various genes associated with CVP defects have been reported. Mesenchymal Fgf10 is essential for the maintenance of Lgr5/Sox2-positive CVP epithelial progenitor cells, which is consistent with the absence of CVP structures in Fgf10-/-mice (Petersen et al, 2011;Zhang et al, 2018). In Pax9 −/− mice, trench formation in CVP and FOP is retarded (Kist et al, 2014).…”

“…To determine whether epithelial folding depends on epithelial cells, reverse recombination was performed at E12.5 for 48 h. As we have shown previously, the CVP epithelium and non-CVP mesenchyme recombination group showed an absence of CVP structure. For rescue experiment, FGF10-soaked beads were implanted in the recombinant CVP epithelium and non-CVP mesenchyme for the maintenance of Lgr5-positive epithelial cells (Zhang et al, 2018). Epithelial folding was observed when CVP epithelium and the mesenchyme were recombined (Figure 3C), but absent when non-CVP epithelium was recombined with CVP mesenchyme (Figure 3D).…”

“…(D') Similar epithelial folding is found in the recombination of CVP epithelium and non-CVP mesenchyme with FGF10-soaked bead. The asterisk indicates the FGF10-soaked beads for the maintenance of Lgr5-positive epithelial stem cells in CVP (Zhang et al, 2018). (E) E12.5 + 48 h cultured control group CVP morphology is similar to E13.5 in vivo.…”

The sense of taste: Development, regeneration, and dysfunction

“…Once the CV placode has been specified, the epithelium undergoes bilateral invaginations into the subjacent lingual epithelium to form the trenches where taste buds will ultimately differentiate (Jitpukdeebodintra et al, 2002;Sohn et al, 2011;S. Zhang et al, 2018;S.…”

“…Zhang, Lee, et al, 2020). FGF, WNT, and HH have been shown to regulate this process, where mesenchymal FGF10 and epithelial WNT and HH function to promote trench invagination (Adhikari et al, 2017;Kim et al, 2009;S. Zhang et al, 2018;S.…”