Expression of IGFBPs in the developing mouse submandibular and von Ebner's glands

The expression of insulin-like growth factor binding proteins (IGFBPs) in the developing mouse submandibular and von Ebner's glands was determined by in situ hybridization and by an immunohistochemical method. In the submandibular glands, IGFBP-2 and IGFBP-4 mRNAs were expressed in the terminal end-buds (TEB) at E13-E17, concomitant with epithelial branching. IGFBP-3 mRNA was expressed in the mesenchyme surrounding the TEB; and IGFBP-5 mRNA, in the ducts. At E17, IGFBP-5 mRNA expression was observed not only in the ducts but also in the TEB. Similarly, IGFBP-4 mRNA expression was observed not only in the TEB but also in the mesenchyme. After birth, IGFBP-4 expression was observed only in the connective tissue and disappeared by P14. That of IGFBP-7 appeared at P1 and was observed in the connective tissue until P21. The IGFBP-5 mRNA expression pattern after birth was the same as that seen at E17, but at P21 IGFBP-5 was immunohistochemically expressed only in the duct. The mRNA level of IGFBP-2 expression at postnatal days was weak, but its protein was detected in the ducts and acini at P14-P21. In von Ebner's glands, which appeared at the base of the circumvallate papillae at E17, only IGFBP-2 and IGFBP-4 mRNAs were expressed in the ducts and acini. Postnatally, IGFBP-4 was substituted by IGFBP-5 in the same region. Immunohistochemically, IGFBP-5 and IGFBP-2 were expressed in the ducts and acini at P14-P21. Throughout the study, IGFBP-6 was not detected by in situ hybridization, the immunoreactivity for it was observed in the nerve fibers of submandibular and von Ebner's glands. These data support a role for these molecules as local mediators of salivary growth and differentiation.