β-Catenin in stromal progenitors controls medullary stromal development

Abstract

The renal stroma is a population of matrix-producing fibroblast cells that serves as a structural framework for the kidney parenchyma. The stroma also regulates branching morphogenesis and nephrogenesis. In the mature kidney, the stroma forms at least three distinct cell populations: the capsular, cortical, and medullary stroma. These distinct stromal populations have important functions in kidney development, maintenance of kidney function, and disease progression. However, the development, differentiation, and maintenance of the distinct stroma populations are not well defined. Using a mouse model with β-catenin deficiency in the stroma cell population, we demonstrate that β-catenin is not involved in the formation of the stromal progenitors nor in the formation of the cortical stroma population. In contrast, β-catenin does control the differentiation of stromal progenitors to form the medullary stroma. In the absence of stromal β-catenin, there is a marked reduction of medullary stromal markers. As kidney development continues, the maldifferentiated stromal cells locate deeper within the kidney tissue and are eliminated by the activation of an intrinsic apoptotic program. This leads to significant reductions in the medullary stroma population and the lack of medulla formation. Taken together, our results indicate that stromal β-catenin is essential for kidney development by regulating medulla formation through the differentiation of medullary stromal cells.