Inactivation of Fam20B in the dental epithelium of mice leads to supernumerary incisors

et al. 2017

Organogenesis

Supernumerary teeth are common clinical dental anomalies. Although various studies have provided abundant information regarding genes and signaling pathways involved in tooth morphogenesis, which include Wnt, FGF, BMP, and Shh, the molecular mechanism of tooth formation, especially for supernumerary teeth, is still unclear. In the population, some cases of supernumerary teeth are sporadic, while others are syndrome-related with familial hereditary. The prompt and accurate diagnosis of syndrome related supernumerary teeth is quite important for some distinctive disorders. Mice are the most commonly used model system for investigating supernumerary teeth. The upregulation of Wnt and Shh signaling in the dental epithelium results in the formation of multiple supernumerary teeth in mice. Understanding the molecular mechanism of supernumerary teeth is also a component of understanding tooth formation in general and provides clinical guidance for early diagnosis and treatment in the future.

Section: DImentioning

confidence: 99%

“…78,79 Pax6 gene homozygous mutant mice or Fam20B null mice showed extra teeth in incisor region. [80][81][82]…”

Section: Supernumerary Teeth In Diastema Regionmentioning

confidence: 99%

The epidemiology of supernumerary teeth and the associated molecular mechanism

et al. 2017

Organogenesis

“…Constitutive inactivation of Fam20B in mice was embryonically lethal, 14 whereas conditional deletion of Fam20B in the rodent dental epithelium led to supernumerary incisors. 15 …”

Section: Introductionmentioning

confidence: 99%

Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth

Xie

et al. 2016

Int J Oral Sci

Self Cite

FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20Aflox/flox mice, we created K14-Cre;Fam20Aflox/flox (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

“…The FAM20B‐dependent phosphorylation of the initial xylose is so critical for the formation of tetrasaccharide linkage that conventional loss of function of Fam20b results in embryonic lethality in mouse and severe deformities in the cartilage and bones of zebrafish . Although we previously reported that inactivation of Fam20b in oral ectoderm led to formation of supernumerary incisors and resulted in compromised enamel , the roles of Fam20b in the development of craniofacial mesenchyme remain largely unknown.…”

mentioning

confidence: 99%

Inactivation of Fam20b in the neural crest‐derived mesenchyme of mouse causes multiple craniofacial defects

European J Oral Sciences

Zhang

et al. 2018

Self Cite

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.