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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. [ABSTRACT FROM AUTHOR]

Dentin sialophosphoprotein (DSPP) is a large precursor protein that is proteolyti-cally processed into a NH2-terminal fragment [composed of dentin sialoprolein (DSP) and a proteoglycan form (DSP-PG)] and a COOH-terminal fragment [dentin phosphoprotein (DPP)]. In vitro studies indicate that DPP is a strong initiator and regulator of hydroxyapatite crystal formation and growth, but the role(s) of the NH2-terminal fragment of DSPP (i.e. DSP and DSP-PG) in dentinogenesis remain unclear. This study focuses on the function of the NH2-terminal fragment of DSPP in dentinogenesis. Here, transgenic (Tg) mouse lines expressing the NHi-lerminal fragment of DSPP driven by a 3.6-kb type I collagen promoter (Col lal) were generated and cross-bred with Dspp null mice to obtain mice that express the transgene but.lack the endogenous Dspp (Dspp KO/DSP Tg). We found that dentin from the Dspp KO/DSP Tg mice was much thinner, more poorly mineralized, and remarkably disorganized compared with dentin from the Dspp KO mice. The fact that Dspp KO/DSP Tg mice exhibited more severe dentin defects than did the Dspp null mice indicates that the NHi-lerminal fragment of DSPP may inhibit dentin mineralization or may serve as an antagonist against the accelerating action of DPP and serve to prevent predentin from being mineralized too rapidly during dentinogenesis [ABSTRACT FROM AUTHOR]