36 research outputs found
The Cellular Prion Protein PrPc Is Involved in the Proliferation of Epithelial Cells and in the Distribution of Junction-Associated Proteins
BACKGROUND: The physiological function of the ubiquitous cellular prion protein, PrP(c), is still under debate. It was essentially studied in nervous system, but poorly investigated in epithelial cells. We previously reported that PrP(c) is targeted to cell-cell junctions of polarized epithelial cells, where it interacts with c-Src. METHODOLOGY/FINDINGS: We show here that, in cultured human enterocytes and in intestine in vivo, the mature PrP(c) is differentially targeted either to the nucleus in dividing cells or to cell-cell contacts in polarized/differentiated cells. By proteomic analysis, we demonstrate that the junctional PrP(c) interacts with cytoskeleton-associated proteins, such as gamma- and beta-actin, alpha-spectrin, annexin A2, and with the desmosome-associated proteins desmoglein, plakoglobin and desmoplakin. In addition, co-immunoprecipitation experiments revealed complexes associating PrP(c), desmoglein and c-Src in raft domains. Through siRNA strategy, we show that PrP(c) is necessary to complete the process of epithelial cell proliferation and for the sub-cellular distribution of proteins involved in cell architecture and junctions. Moreover, analysis of the architecture of the intestinal epithelium of PrP(c) knock-out mice revealed a net decrease in the size of desmosomal junctions and, without change in the amount of BrdU incorporation, a shortening of the length of intestinal villi. CONCLUSIONS/SIGNIFICANCE: From these results, PrP(c) could be considered as a new partner involved in the balance between proliferation and polarization/differentiation in epithelial cells
A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.
BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe
Les maladies rares en odontologie pédiatrique (manifestations cranio-faciales et bucco-dentaires)
LILLE2-BU Santé-Recherche (593502101) / SudocLILLE2-UFR Odontologie (593502202) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
La prévention dentaire en milieu scolaire (réalisation d'une malette éducative destinée aux enfants de 8 à 10 ans)
LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocLILLE2-UFR Odontologie (593502202) / SudocSudocFranceF
Réalisation de fiches conseils pour la prévention chez l'enfant
LILLE2-BU Santé-Recherche (593502101) / SudocLILLE2-UFR Odontologie (593502202) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Enfant, adolescent, obésité et surpoids (conséquences bucco-dentaires à partir d'une étude sur 120 cas)
LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocLILLE2-UFR Odontologie (593502202) / SudocSudocFranceF
La dentisterie restauratrice cosmétique en odontologie pédiatrique
LILLE2-BU Santé-Recherche (593502101) / SudocLILLE2-UFR Odontologie (593502202) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
L'allaitement maternel, quels bénéfices en odontologie pédiatrique ?
LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocLILLE2-UFR Odontologie (593502202) / SudocSudocFranceF
L'odontologie et le sportif (problèmes bucco-dentaires et dopage)
LILLE2-UFR Odontologie (593502202) / SudocLILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Le fluor en odontologie (du cabinet dentaire Ă l'officine)
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF