Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance

Abstract

The adult fungiform taste papilla is a complex of specialized cell types residing in the stratified squamous tongue epithelium. This unique sensory organ includes taste buds, papilla epithelium and lateral walls that extend into underlying connective tissue to surround a core of lamina propria cells. Fungiform papillae must contain long-lived, sustaining or stem cells and short-lived, maintaining or transit amplifying cells that support the papilla and specialized taste buds. Shh signaling has established roles in supporting fungiform induction, development and patterning. However, for a full understanding of how Shh transduced signals act in tongue, papilla and taste bud formation and maintenance, it is necessary to know where and when the Shh ligand and pathway components are positioned. We used immunostaining, in situ hybridization and mouse reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to identify cells that participate in hedgehog signaling. Whereas there is a progressive restriction in location of Shh ligand-expressing cells, from placode and apical papilla cells to taste bud cells only, a surrounding population of Ptch1 and Gli1 responding cells is maintained in signaling centers throughout papilla and taste bud development and differentiation. The Shh signaling targets are in regions of active cell proliferation. Using genetic-inducible lineage tracing for Gli1-expression, we found that Shh-responding cells contribute not only to maintenance of filiform and fungiform papillae, but also to taste buds. A requirement for normal Shh signaling in fungiform papilla, taste bud and filiform papilla maintenance was shown by Gli2 constitutive activation. We identified proliferation niches where Shh signaling is active and suggest that epithelial and mesenchymal compartments harbor potential stem and/or progenitor cell zones. In all, we report a set of hedgehog signaling centers that regulate development and maintenance of taste organs, the fungiform papilla and taste bud, and surrounding lingual cells. Shh signaling has roles in forming and maintaining fungiform papillae and taste buds, most likely via stage-specific autocrine and/or paracrine mechanisms, and by engaging epithelial/mesenchymal interactions.

Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration

“…2F and Fig. S3A), as also noted by others (21)(22)(23)(24). Note that the mG marking of Shh-expressing cells within the taste bud is driven by the CAG promoter inserted at the R26 locus.…”

Histological study of postnatal development of mouse tongues

“…During postnatal stages, the tongue also continually develops, the tongue size increases and the papilla become mature. However, the number, position and ratio of different types of papillae gradually changes to adopt different functions (7,8). The results of the present study also indicated that tongue muscle fibers became larger, mature and stronger during development from newborn to adult mice.…”

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

“…Shh is expressed by Type IV basal cells within adult taste buds, whereas expression of the Shh target genes Gli1 and Ptch1 is restricted to taste progenitors outside of buds (Liu et al, 2013;Miura et al, 2001), prompting the hypothesis that Shh + cells inside taste buds signal to progenitors to regulate taste cell renewal (Miura et al, 2006). In other renewing epithelia, Hedgehog (Hh) functions as a mitogen or a differentiation factor (Lee and Tumbar, 2012;Takashima and Hartenstein, 2012) or can signal to maintain stem cells (Álvarez-Buylla and Ihrie, 2014;Ferent et al, 2014;Saade et al, 2013).…”