Between gestational days 13 and 18 the mouse bladder undergoes smooth muscle differentiation from undifferentiated mesenchyme. The baskin laboratory has shown that induction of bladder smooth muscle occurs through an epithelial signal from the urothelium to the undifferentiated bladder mesenchyme. The signaling appears to be mediated by paracrine signaling molecules emanating from the epithelium to the outer mesenchymal layer. Our key question is: Which gene products from the urothelium control bladder smooth muscle induction? We believe it is relevant that bladder smooth muscle cells first develop in the periphery of the bladder away from the inducing urothelium; the undifferentiated mesenchyme adjacent to the urothelium does not differentiate into smooth muscle.
We hypothesize that select genes differentially expressed before smooth muscle differentiation, rather than those expressed after smooth muscle differentiation, are part of the mechanism that induces bladder smooth muscle formation. Our primary goals is to identify and characterize these inductive genes and their products. As part of accomplishing this goal we have mastered the techniques of isolating the bladder as early as the E12 stage of development in the mouse and of separating bladder epithelium and mesenchyme.