The Formation of Endoderm-Derived Taste Sensory Organs Requires a Pax9-Dependent Expansion of Embryonic Taste Bud Progenitor Cells

Abstract

In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction.

Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling

“…Whereas anterior tongue FPs have an ectodermal embryonic origin, the posterior tongue tissues and large circumvallate papilla (CV) have endodermal derivation [55,56] and could be affected differently by HH/GLI suppression. In contrast to the single TB in rodent FP, the CV contains a few hundred taste buds in dense physical juxtaposition in walls of the papilla trenches [57].…”

Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid

“…That loss of SMO in the interplacodal epithelium of K14-CRE/Smo f/f mutant tongues caused no tongue defects ( S2I–S2J’ Fig ) further demonstrates a temporal requirement for SHH signaling in tongue development. K14-CRE activity in the LE is late onset (≈ E13.5) ( S2K–S2N Fig ) [ 42 ], and taste placodes as well as TBs do not express K14 [ 29 ]. Together, these findings point to a restricted period before E12.5 during which loss of SHH signaling induces tongue defects and support previous findings in rat tongue organ cultures [ 15 ].…”

Pharyngeal arch deficiencies affect taste bud development in the circumvallate papilla with aberrant glossopharyngeal nerve formation

“…Finally, Pax9 ‐/‐ mutants were recently found to display a hypoplastic CV and trench epithelium defects (Kist et al, ). We have shown that Pax9 is a potential target gene of Tbx1 and its expression is modulated by Ripply3 in the PA (Ivins et al, ; Okubo et al, ).…”