Angiogenesis and developmental expression of vascular endothelial growth factor in rat lingual papillae.

We used an embryological approach to investigate development and microvasculature of lingual papillae, and expression of vascular endothelial growth factor (VEGF) in the rat tongue. Temporal changes in the rat tongue at each developmental stage from embryonic day 13 (E13) to postnatal day 7 (P7) were observed by intravascular injection of India ink and immunohistochemistry using a VEGF antibody. At E13, the primordium of circumvallate papilla was observed among various lingual papillae. VEGF was widely expressed at E16 on the proliferated epithelium and the connective tissue core of circumvallate papilla. Invasion by capillary sprouts forming the lingual papillae was observed at E17. The primordium of fungiform papillae was observed at E14. VEGF was strongly expressed around the basal cells of proliferated epithelial tissues of fungiform papillae at E17. At E18, blind-ended capillary sprouts invaded into connective tissue cores from subepithelial sinusoidal capillaries by sprout angiogenesis. At P1, the invading capillary sprouts formed loops by vascular remodeling. The primordium of foliate papillae was observed at E16. VEGF was slightly expressed, but uniformly at E17 on the epithelium, muscle cells, and fibroblasts of foliate papillae. At E18, vascular density was increased by angiogenesis. The primordium of filiform papillae was observed at E17. It was the last to develop among the lingual papillae. VEGF was expressed in the cytoplasm of grown epithelial cells of filiform papillae at E19, and in blind-ended capillary sprouts formed by angiogenesis in the connective tissue cores at E20. The capillary sprouts formed loops by vascular remodeling at P1. Consequently, VEGF was expressed on the papillary epithelium and connective tissue cores of papillae during development of the papillary epithelium, and invasion by capillary sprouts into each papillae was observed thereafter. These results suggest a close relationship between expression of VEGF and angiogenesis of lingual papillae in the rat.