Methods: Lrp4 hypomorphic mutants were analysed by micro CT scanning, histology, immunohistochemistry and in situ hybridization.
Results: Lrp4 showed spatially restricted expression during tooth and palatal rugae development. In Lrp4 mutant mice, molar teeth were fused and the palatal rugae were highly disorganised. Supernumerary teeth and rugae were also present in the mutants. Bmp and Wnt signalling were upregulated while Shh activity was downregulated in fused molars and disorganised palatal rugae. Ectopic expression of Shh was however observed coincident with supernumerary tooth formation in Lrp4 mutants.
Conclusions: The data identify similar molecular and phenotypic changes in tooth and palatal rugae development in Lrp4 mutants and indicate common mechanisms of morphogenesis. Lrp4 thus acts as key cell surface protein integrating multiple signalling pathways that are essential for both tooth and palate morphogenesis.