Activins as regulators of branching morphogenesis

Development of glandular organs such as the kidney, lung, and prostate invo lves the process of branching morphogenesis. The developing organ begins as an epithelial bud that invades the surrounding mesenchyme, projecting divi ding epithelial cords or tubes away from the site of initiation. This is a tightly regulated process that requires complex epithelial-mesenchymal inte ractions, resulting in a three-dimensional treelike structure. We propose t hat activins are key growth and differentiation factors during this process . The purpose of this review is to examine the direct, indirect, and correl ative lines of evidence to support this hypothesis. The expression of activ ins is reviewed together with the effect of activins and follistatins in th e development of branched organs. We demonstrate that activin has both nega tive and positive effects on cell growth during branching morphogenesis, hi ghlighting the complex nature of activin in the regulation of proliferation and differentiation. We propose potential mechanisms for the way in which activins modify branching and address the issue of whether activin is a reg ulator of branching morphogenesis. (C) 2001 Academic Press.