Salivary Gland Morphogenesis

Mouse submandibular salivary gland (SMG) organogenesis is initiated around gestation day 11 and is best conceptualized in stages. In the Prebud Stage, SMG development begins as a thickening of the primitive oral cavity epithelium adjacent to the tongue. During the Initial Bud Stage, the thickening epithelium grows down into the mandibular arch mesenchyme to form the initial SMG bud. Continued proliferation and downgrowth results in a solid epithelial stalk terminating in a bulb. This SMG primordium branches by repeated furcation in the distal ends of successive buds to produce a bush-like structure comprised of a network of epithelial branches and terminal epithelial buds (the Pseudoglandular Stage). These branches and buds hollow out by epithelial cell apoptosis during the Canalicular and Terminal Bud Stages to form the ductal system and presumptive acini. Throughout SMG development, organogenesis is regulated by the functional integration of stage-specific growth-factor-, cytokine-, and transcription factor-mediated signaling which effects specific patterns of cell proliferation, cell quiescence, apoptosis, and histodifferentiation. These molecular effectors interact within the context of a nonlinear genetic network. Our laboratory has done much to elucidate the molecules and the network.