The Cellular Basis of Kidney Development

Abstract

Mammalian kidney development has helped elucidate the general concepts of mesenchymal-epithelial interactions, inductive signaling, epithelial cell polarization, and branching morphogenesis. Through the use of genetically engineered mouse models, the manipulation of Xenopus and chick embryos, and the identification of human renal disease genes, the molecular bases for many of the early events in the developing kidney are becoming increasingly clear. Early patterning of the kidney region depends on interactions between Pax/Eya/Six genes, with essential roles for lim1 and Odd1. Ureteric bud outgrowth and branching morphogenesis are controlled by the Ret/Gdnf pathway, which is subject to positive and negative regulation by a variety of factors. A clear role for Wnt proteins in induction of the kidney mesenchyme is now well established and complements the classic literature nicely. Patterning along the proximal distal axis as the nephron develops is now being investigated and must involve aspects of Notch signaling. The development of a glomerulus requires interactions between epithelial cells and infiltrating endothelial cells to generate a unique basement membrane. The integrity of the glomerular filter depends in large part on the proteins of the nephrin complex, localized to the slit diaphragm. Despite the kidney's architectural complexity, with the advent of genomics and expression arrays, it is becoming one of the best-characterized organ systems in developmental biology.

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

“…The formation of nephrons in the mammalian kidney utilizes several key developmental mechanisms including reciprocal induction of target cells by secreted factors, mesenchymalto-epithelial cell transitions, morphogenesis of epithelial tubules, and patterning of these tubules (Bates, 2007;Costantini, 2006;Dressler, 2006;Yu et al, 2004). The process of nephron formation begins with the outgrowth of the ureteric bud from the Wolffian duct.…”

Pluripotency of Male Germline Stem Cells

“…Sertoli cells secrete GDNF, an essential growth factor for SSC maintenance (Meng et al, 2000). As a member of the TGFβ superfamily of growth factors, GDNF controls kidney development and regulates the survival of many types of neurons (Dressler, 2006;Sariola and Saarma, 2003). Notably, GDNF binds to the GPI-linked receptor GFRα1 on the outer surface of SSCs and mediates the activation of the integral protein 'rearranged during transfection' (RET) tyrosine kinase receptor (Naughton et al, 2006).…”

Role of fibroblast growth factor receptor signaling in kidney development

“…As the ureteric bud elongates, the metanephric mesenchyme divides into a nephrogenic lineage lying adjacent to the bud, and a surrounding renal cortical stromal lineage (that may also have elements of paraxial mesoderm) [8,10]. The kidney continues to develop due to reciprocal inductive interactions, with the ureteric bud receiving signals to branch dichotomously, ultimately to form the collecting ducts and ureters [8]. At each terminal tip, the ureteric bud induces local areas of nephrogenic mesenchyme to differentiate into nephron epithelia, progressing from renal vesicles, to comma-shaped bodies, to Sshaped bodies, and finally to mature nephrons [8].…”

“…The kidney continues to develop due to reciprocal inductive interactions, with the ureteric bud receiving signals to branch dichotomously, ultimately to form the collecting ducts and ureters [8]. At each terminal tip, the ureteric bud induces local areas of nephrogenic mesenchyme to differentiate into nephron epithelia, progressing from renal vesicles, to comma-shaped bodies, to Sshaped bodies, and finally to mature nephrons [8].…”