Branching morphogenesis during kidney development

Epithelial tissues such as kidney, lung, and breast arise through branching morphogenesis of a pre-existing epithelial structure. They share common mo rphological stages and a need for regulation of a similar set of developmen tal decisions-where to start; when, where, and in which direction to branch ; and how many times to branch-decisions requiring regulation of cell proli feration, apoptosis, invasiveness, and cell motility. It is likely that sim ilar molecular mechanisms exist for the epithelial branching program. Here we focus on the development of the collecting system of the kidney, where, from recent data using embryonic organ culture, cell culture models of bran ching morphogenesis, and targeted gene deletion experiments, the outlines o f a working model for branching morphogenesis begin to emerge. Key branchin g morphogenetic molecules in this model include growth factors, transcripti on factors, distal effector molecules (such as extracellular matrix protein s, integrins, proteinases and their inhibitors), and genes regulating apopt osis and cell proliferation.