The MISE Project (Mediation Information System Engineering) aims at providing collaborating organizations with a Mediation Information System (MIS) in charge of supporting interoperability of a collaborative network. MISE proposes an overall MIS design method according to a model-driven approach, based on model transformations. This MIS is in charge of managing (i) information, (ii) functions and (iii) processes among the information systems (IS) of partner organizations involved in the network. Semantic issues are accompanying this triple objective: How to deal with information reconciliation? How to ensure the matching between business functions and technical services? How to identify workflows among business processes? This article aims first, at presenting the MISE approach, second at defining the semantic gaps along the MISE approach and third at describing some past, current and future research works that deal with these issues. Finally and as a conclusion, the very "design-oriented" previous considerations are confronted with "run-time" requirements.