Regulatory role of Six1 in the development of taste papillae.

The Six family genes encode homeobox transcription factors, and their deficiency leads to abnormal sensory organ structures. We analyzed the expression patterns of Six1 and its role in the morphogenesis of taste bud-bearing lingual papillae during mouse embryonic development. Six1 was expressed in the mesenchyme of the lateral lingual swellings at embryonic day (E) 11.5 and in the epithelium of fungiform papillae during E14.5-E17.5. In the posterior region of the tongue, Six1 expression appeared in the epithelial thickenings in the center of the dorsal surface at E13.5-E14.5 and was observed in the trench wall of circumvallate and foliate papillae at E15.5-postnatal day 0. Six1-deficient mice (Six1 (-/-)) showed distinct morphological changes: the fungiform papillae increased in size and number, and their distribution in the tongue differed from that of wild-type mice. The number of primordia of fungiform papillae marked by Shh and Wnt10b appeared to increase in Six1 ( -/- ). With regard to circumvallate papillae, more extensive invagination of epithelial thickenings, earlier formation of papillae, and stunted trenches were noted in Six1 ( -/- ); the expression of Shh was altered, consistent with these anomalies. The foliate papillae were elevated initially and showed stunted trenches in Six1 ( -/- ). Thus, the modulation of signaling events in Six1 ( -/- ) leads to the earlier formation of the gustatory papillae, the abnormal distribution of fungiform papillae, and malformed trenches in circumvallate and foliate papillae.