Résumé
Two opposite actions of DP1 on the Wnt signalling pathway, one negative in the cytoplasm and one positive in the nucleus, contribute to the generation of sharp responses to Wnt gradients.
EMBO J
31
16, 3384–3397 (2012)
Wnt signalling has been under intense scrutiny now for many years, and this effort has led to the identification and characterization of many components, and to a quite satisfactory general picture of the pathway. Yet, as components were discovered at a fast pace and started to crowd around a few scaffold proteins (Axin, APC, Dishevelled, and the main protagonist, β-catenin), the complexity of the system soon became apparent. Thus, behind the simple model presented in all introductions, how the pathway actually works is still far from being fully understood (see, for example, Taelman et al, 2010 and Li et al, 2012). In a context where every molecule seems to be able to interact with every other molecule and single components can perform simultaneously several different reactions, how can one dissect the role of any of them? If everything is so intricate, is there any hope to obtain a satisfactory view of the process? Jho and colleagues' study of one of these molecules, Dimerization Partner 1 (DP1), presented in this issue of The EMBO Journal (Kim et al, 2012), is a beautiful demonstration that this is indeed a reachable goal, although the path is not for the faint of heart! The final result of what probably represents the most comprehensive single study ever published in the field is a coherent description of the dual role of DP1 in Wnt signalling, coupled to the discovery of a new regulatory mechanism involved in refining embryonic patterning.