VEGF-dependent vascular growth promotes dentin secretion from odontoblasts. (A–D) In situ hybridization of mandibular sections. Vegfa mRNA was abundantly expressed in odontoblasts (arrowheads). (E) Protocol for 4OHT injection for Cre induction in Osx-Cre^ERT2 mice and immunohistochemistry at P12. Odontoblasts were clearly marked by Osx-Cre^ERT2 (arrowheads). (F) Immunohistochemistry at P12. Vegfa expression surrounding odontoblasts observed in control mice (closed arrowheads) is not detectable in Osx–Cre^ERT2+Vegfa^flox/flox mice (open arrowheads). (G) Bright-field view of mandibles. Osx–Cre^ERT2+Vegfa^flox/flox mice had impaired molar extrusion (arrowheads). (H–S) Section specimens at P12 and quantification (P, control [Cont] n = 6, Osx–Cre^ERT2+Vegfa^flox/floxn = 6; Q, Cont n = 4, Osx–Cre^ERT2+Vegfa^flox/floxn = 4; R and S, Cont n = 3, Vegfr2^iΔECn = 3). Osx–Cre^ERT2+Vegfa^flox/flox mice exhibited decreased POTCs (open arrowheads in L), increased endothelial apoptosis (arrows), and decreased odontoblast height (open arrowheads in N and O). Scale bars: 500 µm (G); 200 µm (A–D and E [left]); 50 µm (E [right], F, and H–O). Data are presented as means ± SD. Comparisons between two groups were evaluated using a two-sided Student’s t test.