Morphogenesis and molecular mechanisms involved in human kidney development

Abstract

The development of the human kidney is a complex process that requires interactions between epithelial and mesenchymal cells, eventually leading to the coordinated growth and differentiation of multiple highly specialized stromal, vascular, and epithelial cell types. The application of molecular biology and immunocytochemistry to the study of cell types involved in renal morphogenesis is leading to a better understanding of nephrogenesis, which requires a fine balance of many factors that can be disturbed by various prenatal events in humans. The aim of this paper is to review human kidney organogenesis, with particular emphasis on the sequence of morphological events, on the immunohistochemical peculiarities of nephron progenitor populations and on the molecular pathways regulating the process of mesenchymal to epithelial transition. Kidney development can be subdivided into five steps: (i) the primary ureteric bud (UB); (ii) the cap mesenchyme; (iii) the mesenchymal-epithelial transition; (iv) glomerulogenesis and tubulogenesis; (v) the interstitial cells. Complex correlations between morphological and molecular events from the origin of the UB and its branching to the metanephric mesenchyme, ending with the maturation of nephrons, have been reported in different animals, including mammals. Marked differences, observed among different species in the origin and the duration of nephrogenesis, suggest that morphological and molecular events may be different in different animal species and mammals. Further studies must be carried out in humans to verify at the morphological, immunohistochemical, and molecular levels if the outcome in humans parallels that previously described in other species.

Cell Projections and Extracellular Matrix Cross the Interstitial Interface within the Renal Stem/Progenitor Cell Niche: Accidental, Structural or Functional Cues?

“…1a). Interestingly, it contains two different stem/progenitor cell populations [11,12]. Epithelial stem/progenitor cells are localized within the invading ureteric bud.…”

CD44 immunoreactivity in the developing human kidney: a marker of renal progenitor stem cells?

“…6 Another new finding emerging from our study is that CD44 reactivity is not restricted to the nephron lineage, being detected in renal cells of the stromal lineage, including capsular and interstitial cells. 7 The ability of GPECS to dedifferentiate into embryonic phenotype similar to that of myofibroblasts has been previously reported in renal pathology, in the evolution of glomerular crescents. 16 The detection, in this study, of a common CD44 immunoreactivity in glomerular and in interstitial cells in the developing kidney casts some doubt on the origin of renal interstitial cells, suggesting that at least a subset of them might originate from multipotent glomerular cells and not from a stromal progenitor.…”

“…6 To the best of our knowledge, no previous study investigated the role of CD44 during human kidney development, focusing on the expression and distribution pattern of this marker in different renal structures during kidney embryogenesis. 7,8 In this study, we sought to investigate CD44 immunoreactivity during nephrogenesis, in order to verify its expression pattern during mesenchymal to epithelial transition of metanephric mesenchymal cells, as well as its immunostaining in the different sequential structures typically involved in glomerulogenesis and tubulogenesis in the developing human kidney.…”

Böbrek Kök Hücreleri

“…Mezenkim boşluğu renal progenitör hücrelerin mezenkimalden epitel hücrelere dönüştüğü yerdir. Bu progenitör hücreler sonra glomerüler ve renal tübüler yapıların oluşmasına yol açacak olan, sırayla peritübüler agregatlar, renal kesecikler, C ve S formlarını oluşturur (12,13).…”