Bmp signalling in filiform tongue papillae development

ObjectiveTongue papillae are critical organs in mastication. There are four different types of tongue papillae; fungiform, circumvallate, foliate, and filiform papillae. Unlike the other three taste papillae, non-gustatory papillae, filiform papillae cover the entire dorsal surface of the tongue and are important structures for the mechanical stress of sucking. Filiform papillae are further classified into two subtypes with different morphologies, depending on their location on the dorsum of the tongue. The filiform papillae at the intermolar eminence have pointed tips, whereas filiform papillae with rounded tips are found in other regions (anterior tongue). It remains unknown how the shape of each type of filiform papillae are determined during their development. Bmp signalling pathway has been known to regulate mechanisms that determine the shapes of many ectodermal organs. The aim of this study was to investigate the role of Bmp signalling in filiform papillae development.DesignComparative in situ hybridization analysis of six Bmps (Bmp2–Bmp7) and two Bmpr genes (Bmpr1a and Bmpr1b) were carried out in filiform papillae development. We further examined tongue papillae in mice over-expressing Noggin under the keratin14 promoter (K14-Noggin).ResultsWe identified a dynamic temporo-spatial expression of Bmps in filiform papillae development. The K14-Noggin mice showed pointed filiform papillae in regions of the tongue normally occupied by the rounded type.ConclusionsBmp signalling thus regulates the shape of filiform papillae.     

Wnt signaling in the murine diastema

The correct number and shape of teeth are critical factors for an aesthetic and functional dentition. Understanding the molecular mechanisms regulating tooth number and shape are therefore important in orthodontics. Mice have only one incisor and three molars in each jaw quadrant that are divided by a tooth-less region, the diastema. Although mice lost teeth in the diastema during evolution, the remnants of the evolutionary lost teeth are observed as transient epithelial buds in the wild-type diastema during early stages of development. Shh and Fgf signaling pathways that are essential for tooth development have been shown to be repressed in the diastema. It remains unclear however how Wnt signaling, that is also required for tooth development, is regulated in the diastema. In this study we found that in the embryonic diastema, Wnt5a expression was observed in mesenchyme, whereas Wnt4 and Wnt10b were expressed in epithelium. The expression of Wnt6 and Wnt11 was found in both tissues. The Wnt co-receptor, Lrp6, was weakly expressed in the diastema overlapping with weak Lrp4 expression, a co-receptor that inhibits Wnt signaling. Secreted Wnt inihibitors Dkk1, Dkk2, and Dkk3 were also expressed in the diastema. Lrp4 mutant mice develop supernumerary teeth in the diastema that is accompanied by upregulation of Wnt signaling and Lrp6 expression. Wnt signaling is thus usually attenuated in the diastema by these secreted and membrane bound Wnt inhibitors.     

Cole‐Carpenter syndrome in a patient from Thailand

Cole‐Carpenter syndrome (CCS), commonly classified as a rare type of osteogenesis imperfecta, is a disorder with severe bone fragility, craniosynostosis, and distinct facial features. Recently, the heterozygous missense mutation, c.1178A>G, p.Tyr393Cys, in exon 9 of P4HB which encodes protein disulfide isomerase, has been found in three Caucasian patients with CCS. Ethnic background is known to affect clinical manifestations, especially facial features of dysmorphic syndromes. Here, we describe the first Asian CCS patient possessing the recurrent mutation in P4HB. Although she had several common features of CCS including bulging forehead, ocular proptosis, midface hypoplasia, long bone deformity, popcorn epiphyses, vertebral fractures, and scoliosis, she did not have hydrocephalus, wormian bones, and dentinogenesis imperfecta, commonly seen in Caucasian patients. Interestingly, she is the only one without macrocephaly. Radiologically, metadiaphyseal fractures of the long bones with metaphyseal sclerosis were found, substantiating that they provide a definitive radiological feature of CCS. In addition, we showed for the first time a three‐dimensional facial scan of a patient with CCS. She had been given intravenous bisphosphonate since the age of 9 months and had responded well. Our study presents the clinical features of the first Asian patient, supports metaphyseal scleroses and fractures as radiological clues, strengthens early bisphosphonate administration, and confirms the etiologic role of the c.1178A>G variant in P4HB across populations.