Int. J. Dev. Biol. In Press
doi: 10.1387/ijdb.200307lg
© UPV/EHU Press

Canonical Wnt signaling regulates branching morphogenesis of submandibular gland by modulating levels of lama5

Liming Gou*,1,2, Xiaochun Ren1,2, Ping Ji*,1,2

1Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences and 2Department of Oral and Maxillofacial Surgery, the Stomatological Hospital of Chongqing Medical University, Chongqing, China

ABSTRACT Background: Branching morphogenesis is a crucial developmental mechanism for the formation of a typical bush-like structure of the submandibular gland (SMG). However, the detailed mechanism underlying this process remains to be fully understood. Here, we investigate whether a cross-talking may exist between Wnt/beta-catenin signaling pathway and lama5 during the branching process in SMG development. Methods: Embryonic mouse SMG organ culture model was established, and the validity of this model was confirmed. The roles of Wnt/beta-catenin signaling pathway, FGF signaling, and Lama5 in the branching process were investigated by morphogenesis assays. And the interactions between these signaling were also investigated and demonstrated by morphogenesis assays and gene expression patterns. Results: We demonstrated that E12 or E13 SMG organ culture model can be used as an ideal approach to study the process of branching morphogenesis. And branching morphogenesis assay revealed that the epithelial branching process would be promoted when the canonical Wnt pathway was inhibited and be significantly suppressed when wnt pathway is over activated. Further experiments indicated that FGF signaling acts most likely acts upstream as a negative regulator of the canonical Wnt pathway during the branching process, whose effect could be partially reversed by Wnt3a. And we further demonstrated that Wnt/beta-catenin signaling regulates the branching morphogenesis through Lama5. Conclusion: Our present work demonstrated that Wnt/beta-catenin signaling pathway acting downstream of FGF signaling may serve as a negative regulatory mechanism in the process of SMG branching morphogenesis through Lama5.

Keywords:

Salivary gland, Branching morphogenesis, Organ culture, Wnt/β catenin signal transduction pathway, Laminin

*Corresponding author e-mail: goulm@hospital.cqmu.edu.cn ; jiping@hospital.cqmu.edu.cn