Bcl11b/Ctip2 is required for development of lingual papillae in mice.

Molecular mechanisms underlying the development and morphogenesis of oral epithelia, comprising the gustatory and nongustatory epithelium, remain unclear. Here, we show that Bcl11b, a zinc finger transcription factor, plays an important role in the development of lingual papillae, especially filiform papillae. In both gustatory and nongustatory epithelium, Bcl11b was expressed in keratin 14-positive epithelial basal cells, which differentiate into keratinocytes and/or taste cells. Loss of Bcl11b function resulted in abnormal morphology of the gustatory papillae: flattened fungiform papillae, shorter trench wall in the foliate and circumvallate papillae, and ectopic invagination in more than half of circumvallate papillae. However, Bcl11b loss caused no effect on differentiation of taste receptor cells. In nongustatory epithelium, the impact of Bcl11b deficiency was much more striking, resulting in a smooth surface on the tongue tip and hypoplastic filiform papillae in the dorsal lingual epithelium. Immunohistochemical analyses revealed that a keratinocyte differentiation marker, Tchh expression was severely decreased in the Bcl11b(-/-) filiform papillae. In addition, expression of Pax9, required for morphogenesis of filiform papillae and its downstream target genes, hard keratins, almost disappeared in the tongue tip and was decreased in the dorsal tongue of Bcl11b(-/-) mice. Gene expression analyses demonstrated a delayed onset of expression of epithelial differentiation complex genes, which disturbed barrier formation in the mutant tongue. These results indicate that Bcl11b regulates the differentiation of keratinocytes in the tongue and identify Bcl11b as an essential factor for the lingual papilla morphogenesis.

Genetic Lineage Tracing in Taste Tissues Using Sox2-CreERT2 Strain.

Taste cells in taste buds are epithelial sensory cells. Old taste bud cells die and are replaced by new ones generated from taste stem cells. Identifying and characterizing adult taste stem cells is therefore important to understand how peripheral taste tissues are maintained. SOX2 is expressed in oral epithelium including gustatory papillae and has been proposed to be a marker of adult taste stem/progenitor cells. Nevertheless, this hypothesis has never been directly tested. Here, by single-color genetic lineage tracing using Sox2-CreERT2 strain, we reveal that all types of taste bud cells distributed throughout the oral epithelium are derived from stem cells that express SOX2. Short-term tracing shows that SOX2-positive taste stem cells actively supply taste bud cells. At the base of epithelium outside taste buds are distributed proliferation marker- and SOX2-positive cells. Consistently, taste stem cells identified by Lgr5 expression in the circumvallate papillae also express SOX2. Together, taste stem cells distributed in oral epithelia express SOX2.