Objectif During spermatogenesis, germ cells located in the basal compartment of the seminiferous epithelium of the testis migrate across the blood-testis barrier (BTB) to continue differentiation on the luminal side. This trans-epithelial migration (TEM) requires regular restructuring of junctions present in the BTB. How germ cells pass the BTB, which harbours one of the tightest junctions present in the body, without compromising the integrity of the BTB is poorly understood. Several hypotheses have been put forward, but the mechanism remains unknown. We have recently published evidence for the existence of an intermediate compartment harbouring germ cells in transit across the BTB. This compartment is composed of the tight junction proteins occludin, claudin-3 and CAR. Claudin-3 and CAR appear to be unique to the intermediate compartment since these proteins are not general components of the BTB, and could therefore be used as biological markers. This application is based on these findings. We plan to use several different innovative approaches to uncover mechanisms for TEM and the role of the intermediate compartment in this process. 3D reconstructions of germ cells during TEM will be produced using several imaging techniques including the novel and powerful method of Dual Beam Microscopy. Integrity across the BTB will be analyzed by using tracers of defined size, protein composition of the intermediate compartment will be analyzed using a combination of imaging and gene expression tools and an in vitro model system will be set up using primary cells isolated from testis. Finally, the role of CAR in TEM will be analysed using a conditional CAR knockout mouse that was recently constructed in our laboratory. We expect that results will lead to new insights into mechanisms governing transit of germ cells across the BTB. The study will also be of general interest to reproductive biologists analysing male infertility and to researchers developing new male contraceptives. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopy Mots‑clés CAR CTX blood-testis barrier coxsackievirus and adenovirus receptor endocrinology spermatogenesis testis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships" Appel à propositions FP7-PEOPLE-2007-4-2-IIF Voir d’autres projets de cet appel Régime de financement MC-IIF - International Incoming Fellowships (IIF) Coordinateur KAROLINSKA INSTITUTET Contribution de l’UE € 223 172,25 Adresse Nobels Vag 5 17177 Stockholm Suède Voir sur la carte Région Östra Sverige Stockholm Stockholms län Type d’activité Higher or Secondary Education Establishments Contact administratif Thomas Walstam (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire LUDWIG INSTITUT FUR KREBSFORSCHUNG AG Participation terminée Suisse Contribution de l’UE € 19 500,00 Adresse STADELHOFERSTRASSE 22 8001 ZURICH Voir sur la carte Région Schweiz/Suisse/Svizzera Zürich Zürich Type d’activité Research Organisations Contact administratif Charlotta Linderholm (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée