Sox9 contributes to postnatal opening of the murine parotid papilla

The parotid papilla is the epithelial outlet through which the parotid duct opens into the oral cavity. Although the papilla is thought to open postnatally, its precise timing and morphogenetic events during the initial opening have not been anatomically defined. Sox9 is essential for salivary gland development; however, its role in parotid papilla formation and opening remains unclear. Here, we (i) determined when and how the parotid papilla opens after birth and (ii) tested whether Sox9 is required for this process. We analyzed C57BL/6 J mice at postnatal days (P) 2-6 and Sox9CreER;Sox9^fl/+ mice following tamoxifen administration at P2. In wild-type mice, the parotid papilla opened into the oral cavity at P4. Immediately prior to opening (P2-P3), Sox9-high epithelial cells transiently accumulated within the papillary epithelium and rapidly decreased after opening. In Sox9CreER;Sox9^fl/+ mice, papilla opening was absent at P5 and the papilla itself displayed marked hypoplasia. These findings demonstrate that Sox9 haploinsufficiency disrupts parotid papilla morphogenesis and impairs the formation of a patent salivary duct outlet, thereby providing an anatomical basis for the postnatal opening of the parotid papilla.