From ureteric bud to the first glomeruli: genes, mediators, kidney alterations

Abstract

The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.

Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study

“…42 Fetal kidneys develop through “branching morphogenesis,” which reaches peak growth during the third trimester. 43 44 Preterm birth interrupts this critical growth process, resulting in a lower nephron number as well as a higher percentage of abnormal glomeruli. 45 46 In addition, potentially nephrotoxic drugs commonly used in the treatment of preterm infants might impair postnatal nephrogenesis.…”

When morphogenetic proteins encounter special extracellular matrix and cell-cell connections at the interface of the renal stem/progenitor cell niche

“…Extension of parenchyma is further based on a specific spatiotemporal program conducted by numerous stem/progenitor cell niches each containing cells of the metanephric mesenchyme and epithelial cells [ 2 , 3 ]. The occurrence of epithelial stem/progenitor cells is special, since they are concentrated during anlage of a kidney in the ureteric bud, while during subsequent radial growth of parenchyma they are recognized in the tip of a bud-derived collecting duct (CD) ampulla [ 4 , 5 ]. In contrast, mesenchymal stem/progenitor cells are grouped around the tip of an ampulla so that they are always exposed to the basal aspect of epithelial cells [ 6 ].…”

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

“…The preterm-born individual's kidney function will depend on the effective nephron mass, which is proportional to the number of perfused and fully formed glomeruli (47). The kidneys form in parallel with other organ systems by a process of branching morphogenesis (48)(49)(50). Among the organ systems that develop by branching morphogenesis are the lungs, pancreas, vascular tree and kidneys, which share genetic and physiologic functional determinants within the fetal origins of adult disease paradigm (51)(52)(53).…”