Role of IGFBPs in the morphogenesis of lingual papillae

The expression of insulin‐like growth factor binding proteins (IGFBPs) during the morphogenesis of lingual papillae of mice was examined by in situ hybridization. Among seven mouse IGFBPs, IGFBP‐1, ‐6, and ‐7 mRNAs were not expressed in the tongue tissue. At E12, though no papillae have formed yet, IGFBP‐2, ‐4, and ‐5 were expressed in the entire tongue epithelium. At E14, fungiform papillae appeared in the anterior region and circumvallate papillae were distinguished in the posterior region. Strong expression of IGFBP‐5 was observed in the apical region of both fungiform and circumvallate papillae. At this stage, the epithelial elevation of filiform papillae was not clear; but IGFBP‐5 was expressed in the apex. At E15, foliate papillae were distinguished and IGFBP‐5 was expressed in the dorsal epithelium of ridges. In filiform papillae, IGFBP‐3 was expressed in the core of the connective tissue. At E17, the expression of IGFBP‐5 disappeared from the apical region of fungiform, filiform, foliate, and circumvallate papillae, whereas that of IGFBP‐2 remained. This finding suggests that IGFBP‐5 and ‐2 function to cause evagination of the epithelium into a raised structure. In the epithelium of trenches of foliate and circumvallate papillae, strong expression of IGFBP‐4 was observed at E15 and E17. As previously suggested from a study on postnatal mice (Suzuki et al. J Comp Neurol 2005;482:74–84), IGFBP‐4 acts in the epithelial invagination to form the trenches, grooves, or furrows of lingual papillae during development. © 2005 Wiley‐Liss, Inc.