The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans exert multiple roles, such as enriching signal molecules and regulating the binding of ligands to the corresponding receptors. A newly identified kinase - family with sequence similarity 20 member B (FAM20B) - is essential for the formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on the side chain of a serine residue in the protein. Although the GAG chains of proteoglycans are believed to be indispensable during craniofacial development, there are few reports on their exact functions in craniofacial organogenesis. In this study, by mating Wnt1-cre mice with Fam20b-floxed mice (Fam20bflox/flox), we created Wnt1-Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural crest-derived mesenchyme. The Wnt1-Cre;Fam20bflox/flox mice died immediately after birth because of complete cleft palates. In addition to cleft palate, Wnt1-Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia, microcephaly, suture widening, and reduced mineralization in the calvaria, facial bones, and temporomandibular joint. These findings indicate that the proteoglycans formed through the catalysis of FAM20B are essential for the morphogenesis and mineralization of the craniofacial complex.

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Family with sequence similarity 20, member A (Fam20a) encodes a pseudokinase which is regarded to facilitate the role of Fam20c in phosphorylating secreted proteins. Fam20c deficiency causes Raine Syndrome in human and impaired the amelogeneis, dentiogenesis and osteogenesis in mice. Mutations in Fam20a are associated with Amelogenesis Imperfecta and Enamel-Renal Syndrome in human. Similarly, abrogation of Fam20a in ectoderm caused Amelogeneis Imperefeca in mice, however, the global knock-out of Fam20a in mice showed few anomaly in dentin and bone. In this study, the Fam20a LacZ mice showed that at the E17.5, the LacZ staining was located in the osteogenic lining of calvarium and mandibular bone, odontoblasts, ameloblasts, the gingival and subcutaneous fibroblasts. During the postnatal life, the LacZ staining was detected in the osteogenic and gingival cells in mandibular bone, as well as the osteogenic and the marrow cells in long bone, but excluded from the joint cartilage. Both the LacZ staining in the mandibular and long bone became faint with the life increased. To address if Fam20a is required for the role of Fam20c during the dentinogenesis and osteogenesis, we first examined the mandibular bone and femur of the Wnt1-cre;Fam20a f/f , Osr2-cre;Fam20a f/f and Col1-cre; Fam20a f/f mice. The gross views and X-ray plain images showed no difference in the tissue morphology and mineralization density between these conditional knock-out mice and their controls. Our findings suggested that Fam20a was not required by Fam20c during dentinogenesis and osteogenesis.