Regulation of tissue regeneration and cell fate by the apical-lateral polarity complex

A complex network of polarity proteins sets up the apicobasal polarity axis in epithelial cells, in adult tissues and in the embryo at early stages of development. The architectural role of these complexes has been extensively studied. For instance, they are required for the initiation and the maintenance of junctional complexes such as tight junctions. Their loss or deregulation therefore results in tissue disorganisation and is thought to be involved in cancer development. However, it is now emerging that, the function of polarity complexes goes beyond their structural role and they may instead actively take part in signal transduction to maintain tissue homeostasis and direct cell fate decisions.  Recently, we identified the tumour suppressor  ASPP2  as an important polarity protein.  ASPP2  establishes the apicobasal polarity axis by interacting with Par3 and ensures its proper localisation at the apical-lateral domain corresponding to tight junctions in epithelial cells. This is of particular importance during central nervous system development, as  ASPP2  regulates the polarity of radial glial cells.  In addition to describing the structural role of the  ASPP2 /Par3 apical-lateral polarity complex, I will discuss how it is mechanistically involved in signal transduction by interacting with a phosphatase and one of the main effectors of the Hippo pathway,  YAP . I will discuss how this may be of particular relevance during tissue regeneration and early cell fate decisions by presenting examples in the context of colon regeneration following  DSS -induced colitis and trophectoderm differentiation during pre-implantation development.

If you have a question about this talk, please contact Sarah Noujaim.