The Magic School bus – Ms. Frizzle(d) plunges into the underlying mechanisms of developmental disorders affecting the Wingless pathway

Synopsis

Embryonic morphogenesis is one of the main themes studied in the Richman lab. We try to unravel the coordinated processes that lead to formation of the face and limb using a variety of approaches in the chicken embryo model. In the presentation, the starting point is a rare human disease, Robinow Syndrome, in which the genetic basis is abnormal Wingless signaling (caused by mutations in WNT, Frizzled and Disheveled). At the earliest stages studied, we found long range and symmetrical communication between facial mesenchymal cells is disrupted when a signaling cascade downstream of WNT is inhibited. When we introduce the WNT mutations into the chicken limb or face and let the structures develop, we find that the main target tissue is the forming skeleton. In this talk we will reveal how WNT signaling is used to set up polarity in the skeleton and than when WNT pathway  mutations are present, the skeleton is incapable of elongating or differentiating normally. Finally we suggest that the basis of Robinow Syndrome is likely dominant-negative interaction between the mutant and normal proteins.