Neurturin Influences Epithelial Branching Morphogenesis in the Mouse Submandibular Gland

Neurturin is a neurotrophic growth factor produced by the mouse submandibular gland (SMG) epithelium. It binds to its receptor GFRa2 in the neurons of the parasympathetic submandibular ganglion (PSG). The PSG produces acetylcholine which binds to muscarinic receptors on both the nerves and the epithelium. Objectives: Our hypothesis is that neurturin production and signaling influences epithelial branching morphogenesis in the embryonic mouse SMG. Methods: Embryonic day 12 (E12) SMGs were cultured for 48 hours with treatments of either rabbit IgG as a control or with varying doses of a function-blocking anti-neurturin antibody. The amount of branching morphogenesis was quantitated by counting the number of epithelial end buds. Gene expression of muscarinic receptors, GFRa2, and other genes that are related to SMG morphogenesis were analyzed by real time PCR. Results: The branching of the glands was decreased compared with control with the anti-neurturin treatment of 50ug. In addition, the expression of muscarinic receptors were increased when neurturin function was decreased. Conclusion: Our results suggest that neurturin influences epithelial morphogenesis in the SMG and neurturin signaling alters expression of muscarinic receptor genes, which are possibly involved in both neuronal and epithelial growth and signaling.