Patterning of papillae on the mouse tongue: a system for the quantitative assessment of planar cell polarity signaling.

Abstract The dorsal surface of the mouse tongue is covered by ~7000 papillae, asymmetric epithelial protrusions that are precisely oriented to create a stereotyped macroscopic pattern. Within the context of this large-scale pattern, neighboring papillae exhibit a high degree of local order that minimizes the differences in their orientations. We show here that the orientations of lingual papillae are under the control of the core planar cell polarity (PCP) genes Vangl1 , Vangl2 , and Celsr1 . Using K14-Cre and Nkx2.5-Cre to induce conditional knockout of Vangl1 and/or Vangl2 in the tongue epithelium, we observe more severe disruptions to local order among papillae with inactivation of larger numbers of Vangl genes, a greater role for Vangl2 than Vangl1 , and a more severe phenotype with the Vangl2 Looptail ( Lp ) allele than the Vangl2 null allele, consistent with a dominant negative mode of action of the Vangl2 Lp allele. Interestingly, Celsr1 −/− tongues show disruption of both local and global order, with many papillae in the anterior tongue showing a reversed orientation. To quantify each of these phenotypes, we have developed and applied three procedures for sampling the orientations of papillae and assessing the degree of order on different spatial scales. The experiments reported here establish the dorsal surface of the mouse tongue as a favorable system for studying PCP control of epithelial patterning.