beta-catenin/TCF/Lef controls a differentiation-associated transcriptional program in renal epithelial progenitors.

In the embryonic kidney, progenitors in the metanephric mesenchyme differentiate into specialized renal epithelia in a defined sequence characterized by the formation of cellular aggregates, conversion into polarized epithelia and segmentation along a proximal-distal axis. This sequence is reiterated throughout renal development to generate nephrons. Here, we identify global transcriptional programs associated with epithelial differentiation utilizing an organ culture model of rat metanephric mesenchymal differentiation, which recapitulates the hallmarks of epithelialization in vivo in a synchronized rather than reiterative fashion.

Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2.

Wnts are lipid-modified secreted glycoproteins that regulate diverse biological processes. We report that Wnt5a, which functions in noncanonical Wnt signaling, has activity on endothelial cells. Wnt5a is endogenously expressed in human primary endothelial cells and is expressed in murine vasculature at several sites in mouse embryos and tissues.

Wnt/Frizzled signaling in the vasculature: new angiogenic factors in sight.

Wnt growth factors function via Frizzled receptors to affect cellular proliferation, differentiation, apoptosis, and migration. Wnt/Frizzled signaling is now linked to human hereditary disorders with retinal vascular defects, implicating Wnts as angiogenic factors. Here, we discuss Wnts and a novel Frizzled ligand, Norrin, in physiological and pathological angiogenesis.

Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells.

Wnts are secreted signaling proteins able to control diverse biological processes such as cell differentiation and proliferation. Many Wnts act through a canonical, beta-catenin signaling pathway. Here, we report that Wnt receptors and transcriptional effectors are expressed in primary human endothelial cells and that Wnt/beta-catenin signaling promotes angiogenesis.

Beta-catenin/Tcf activation partially mimics the transforming activity of Wnt-1 in Rat-1 fibroblasts.

We have previously demonstrated that Wnt-1 induction of cytosolic beta-catenin and Tcf/Lef transcriptional activation correlate with enhanced proliferation, survival, and post-confluent growth in Rat-1 fibroblasts. To examine whether beta-catenin mediates the biological responses to Wnt-1 in this context, we characterized Rat-1 clonal cell lines expressing different levels of a mutant, stabilized beta-catenin (beta-cateninS37A). Clonal lines exhibit elevated cytosolic and nuclear beta-cateninS37A and Tcf transcriptional activation, comparable to that elicited by Wnt-1 expression.