The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia

AbstractHypoxia is a common pathogenic stress, which requires adaptive activation of the Hypoxia-inducible transcription factor (HIF). In concert transcriptional HIF targets enhance oxygen availability and simultaneously reduce oxygen demand, enabling survival in a hypoxic microenvironment. Here, we describe the characterization of a new HIF-1 target gene, Rab20, which is a member of the Rab family of small GTP-binding proteins, regulating intracellular trafficking and vesicle formation. Rab20 is directly regulated by HIF-1, resulting in rapid upregulation of Rab20 mRNA as well as protein under hypoxia. Furthermore, exogenous as well as endogenous Rab20 protein colocalizes with mitochondria. Knockdown studies reveal that Rab20 is involved in hypoxia induced apoptosis. Since mitochondria play a key role in the control of cell death, we suggest that regulating mitochondrial homeostasis in hypoxia is a key function of Rab20. Furthermore, our study implicates that cellular transport pathways play a role in oxygen homeostasis. Hypoxia-induced Rab20 may influence tissue homeostasis and repair during and after hypoxic stress

Amélogenèses imparfaites héréditaires, Msx2 et protéines de l'émail

Les amélogenèses imparfaites héréditaires sont des pathologies affectant la structure et la minéralisation de l émail des dents. Des mutations ont été décrites dans des gènes codant des protéines de structure (AMELX, ENAM), des enzymes de la maturation de l émail (KLK4, MMP2O) et des facteurs de transcription (DLX3, MSX2). Afin d étudier la physiopathologie de ces altérations amélaires, nous avons analysé un modèle de souris knock-in Msx2. Nos travaux ont ainsi révélé que Msx2 est le gène candidat d un syndrome associant amélogenèse imparfaite, retards d éruption et calcifications ectopiques notamment rénales. Nos résulats montrent également le rôle de Msx2 dans la régulation de la différenciation des cellules épithéliales et de l expression des protéines de l émail. Dans une dernière partie, nous avons analysé l expression des protéines de l émail dans différents tissus osseux de la mandibule et du tibiaPARIS7-Odontologie (751062104) / SudocSudocFranceF

Caractérisation cytogénétique et moléculaire d' un nouveau sous-type de cancers du sein canalaires

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Targeted expression of the only zinc finger gene in transgenic mice is associated with impaired mammary development.

International audienc

Enamel Protein Regulation and Dental and Periodontal Physiopathology in Msx2 Mutant Mice

Signaling pathways that underlie postnatal dental and periodontal physiopathology are less studied than those of early tooth development. Members of the muscle segment homeobox gene (Msx) family encode homeoproteins that show functional redundancy during development and are known to be involved in epithelial-mesenchymal interactions that lead to crown morphogenesis and ameloblast cell differentiation. This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult. The analysis focused on enamel and periodontal defects and enamel proteins in Msx2-null mutant mice. In the epithelial lifecycle, the levels of MSX2 expression and enamel protein secretion were inversely related. Msx2+/− mice showed increased amelogenin expression, enamel thickness, and rod size. Msx2−/− mice displayed compound phenotypic characteristics of enamel defects, related to both enamel-specific gene mutations (amelogenin and enamelin) in isolated amelogenesis imperfecta, and cell-cell junction elements (laminin 5 and cytokeratin 5) in other syndromes. These effects were also related to ameloblast disappearance, which differed between incisors and molars. In Msx2−/− roots, Malassez cells formed giant islands that overexpressed amelogenin and ameloblastin that grew over months. Aberrant expression of enamel proteins is proposed to underlie the regional osteopetrosis and hyperproduction of cellular cementum. These enamel and periodontal phenotypes of Msx2 mutants constitute the first case report of structural and signaling defects associated with enamel protein overexpression in a postnatal context