Global approach of transcriptome in the alveolar bone of a knock-in Msx2-/- murine model.

Vertebrate Muscle Segment homeobox genes (Msx) control development. Their functions in post-natal growth and homeostasis remain unexplored. The present project is dedicated to Msx2 in post-natal tooth and bone oral physiopathology. Arjeta Agailiu thesis (directed by Pr. Ariane Berdal) aims to provide the molecular phenotype profiles of forming cells for dental tissues and associated bone, as well as their regulatory pathways relied to Msx2. A transgenic Msx2 knock-in mouse line is used. Msx2-/- mice exhi bit pleiotropic defects in the skull, tooth, alveolar bone and several epithelial mesenchymal systems. Msx2 targets will be identified by comparing alveolar bone transcriptome in Msx2 -/-, Msx2 +/- and Msx2 +/+ mice. In Paris, a dozen of effectors (enamel proteins, RANK ligand, BMPs) have been identified as Msx2-targets by a « gene by gene » strategy. But, this method does not permit to discover unknown pathways. This project will provide original results with cDNA microarrays and bioinformatic analysis of affected pathways, routinely performed by the Oslo group. Indeed, nowadays, the global transcriptome approach is the gold standard strategy to delineate molecular basis of distinct biological processes. Oslo team has already applied this strategy to de velopment in oral cells (mouse molars germs and salivary glands). This bilateral project is focused on overlapping Paris/Oslo team interests (transcription factors, non coding RNAs, oral physiopathology). In Paris, we have developped microdissection proto cols. Oslo team is interested in developping this approach to cellular subpopulations (ameloblasts, odontoblasts, alveolar bone osteoblasts) issued from Paris skill. Our overall aim is to facilitate mutual exchanges and built-up a collaborative program to be submitted to EEC funding application. A one-month support is required for analysis of Msx2 pathways in the Institute of Oral Biology, under the direction of Pr. Harald Osmundsen.