Abstract
Bclโ2 is the founding member of a family of proteins that influence apoptosis. During kidney development bclโ2 not only acts as a survival factor, but may also impact cell adhesive mechanisms and by extension branching morphogenesis. The interrelationship between cell adhesion, migration and apoptosis, important during development, is poorly understood. Here we examined the impact lack of bclโ2, an inhibitor of apoptosis, has on ureteric bud (UB) cell adhesion, migration, and branching morphogenesis. Bclโ2 โ/โ UB cells demonstrated increased cell migration, increased cell invasion and decreased adhesion to vitronectin and fibronectin compared with wildโtype cells. Bclโ2 +/+ UB cells readily branched in collagen gel and Matrigel while bclโ2 โ/โ UB cells did not undergo significant branching in either matrix. Reโexpression of bclโ2 in bclโ2 โ/โ UB cells restored their ability to undergo branching morphogenesis in Matrigel. Consistent with our in vitro data, we show that in the absence of bclโ2, embryonic kidneys undergo decreased UB branching. We observed decreased numbers of UB branch points, UB branch tips and a decreased distance to the first UB branch point in the absence of bclโ2. The alterations in bclโ2 โ/โ UB cell adhesion and migration was also associated with a significant alteration in expression of a number of extracellular matrix proteins. Bclโ2 โ/โ UB cells exhibited increased fibronectin expression and decreased thrombospondinโ1 and osteopontin expression. Taken together, these data suggest that bclโ2 is required for the proper regulation of cell adhesive and migratory mechanisms, perhaps through modulation of the cellular microenvironment. J. Cell. Physiol. 210: 616โ625, 2007. ยฉ 2006 WileyโLiss, Inc.