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 morphological stages and a need for regulation of a similar set of developmental decisions--where to start; when, where, and in which direction to branch; and how many times to branch--decisions requiring regulation of cell proliferation, apoptosis, invasiveness, and cell motility. It is likely that similar 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 branching morphogenesis, and targeted gene deletion experiments, the outlines of a working model for branching morphogenesis begin to emerge. Key branching morphogenetic molecules in this model include growth factors, transcription factors, distal effector molecules (such as extracellular matrix proteins, integrins, proteinases and their inhibitors), and genes regulating apoptosis and cell proliferation.