Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

Abstract

While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches.

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

“…The nephrogenic zone of a fetal kidney is a narrow band along the entire inner side of the renal capsule that contains a lot of progenitor cells and undergoes continuous attenuation during kidney development [39]. The width of the nephrogenic zone, which is inversely correlated to gestational age, is considered to indicate the state of ongoing nephrogenesis [40].…”

The mutual patterning between the developing nephron and its covering tissues—valid reasons to rethink the search for traces left by impaired nephrogenesis

“…1 and 4 ). Earlier investigations revealed that the tip of the CD ampulla does not contact the inner side of the renal capsule but stays in an average distance of 32 µm [ 8 ]. In the space between, only 2 to 3 cell layers of mesenchymal progenitor cells are detected.…”

“…Although surprisingly, the analysis of pertinent literature further revealed that the role of the nephrogenic zone in the fetal human kidney in nephron formation and consequently as the primary target region for noxae impairing nephrogenesis has been hardly explored. Before this background, it is understandable that the contained stages of nephron anlage and the shaping of the nephron were only introduced over the past few years as the first systematic morphological information dealing with the specifics of the nephrogenic zone [ 8 – 10 ]. The results generated indicate that each stage of nephron anlage is the subject of an individual positioning, orientation, and shaping.…”

“…1 a and 2 a). Only 2 to 3 layers of mesenchymal progenitor cells are seen here [ 8 ]. For the rodent kidney, it was shown that these layers are arranged in a topological order.…”

“…The formation of a nephron is initiated by the process of induction. This takes place in a nephrogenic niche and within close proximity to the inner side of the renal capsule [ 8 ]. During this process, the most inner layer of the nephrogenic progenitor cells faces the basal aspect of the epithelial progenitor cells contained in the ureteric bud-derived tip of a CD ampulla.…”