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Principles of human and mouse nephron development

Abstract

The mechanisms underlying kidney development in mice and humans is an area of intense study. Insights into kidney organogenesis have the potential to guide our understanding of the origin of congenital anomalies and enable the assembly of genetic diagnostic tools. A number of studies have delineated signalling nodes that regulate positional identities and cell fates of nephron progenitor and precursor cells, whereas cross-species comparisons have markedly enhanced our understanding of conserved and divergent features of mammalian kidney organogenesis. Greater insights into the complex cellular movements that occur as the proximal–distal axis is established have challenged our understanding of nephron patterning and provided important clues to the elaborate developmental context in which human kidney diseases can arise. Studies of kidney development in vivo have also facilitated efforts to recapitulate nephrogenesis in kidney organoids in vitro, by providing a detailed blueprint of signalling events, cell movements and patterning mechanisms that are required for the formation of correctly patterned nephrons and maturation of physiologically functional apparatus that are responsible for maintaining human health.

Key points

  • The gradual recruitment of nephron progenitors prefigures positional identities in the developing nephron.

  • Differentiating cells positioned along the proximal–distal axis of the early nephron display characteristics of mature cell types, indicating the existence of precursor–progeny relationships.

  • The process of nephrogenesis is intricately controlled by a number of signalling pathways, including those involving Notch, WNT, BMP and FGF.

  • Nephrogenesis is highly conserved between human and mouse, indicating an ancient evolutionary origin.

  • Podocytes and epithelial tubular components of the nephron display distinct transcriptional signatures and form at different times during nephrogenesis.

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Fig. 1: Nephron progenitor movements and a hierarchical ordering to the nephrogenic niche.
Fig. 2: The gradual recruitment model of nephrogenesis.
Fig. 3: The gradual recruitment of cells into the nephron and formation of putative precursor domains.
Fig. 4: Abundance of the Notch ligand JAG1 abundance throughout nephron development as a lineage map.

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Acknowledgements

The authors are grateful to all members past and present in the Lindström laboratory, and to A. McMahon for his mentorship. J.S. is funded by a T32 training grant. M.A.A. and N.O.L. are funded by the University of Southern California, USA.

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Supplementary information

Glossary

Filopodia

Dynamic, thin cell-membrane protrusions associated with cell sensing and migration.

Lamellipodia

Dynamic, broad cell-membrane protrusions associated with cell migration.

Planar cell polarity

An axial dimension associated with the plane within an epithelium and elsewhere used in association with a pathway.

Maturity-onset diabetes of the young

A rare form of genetically linked diabetes with an early onset.

Chromatin immunoprecipitation

(ChIP). A laboratory technique used to isolate DNA bound by transcription factors and other DNA-binding proteins using antibodies against these proteins.

Fanconi renotubular syndrome

(FRTS). A rare disorder associated with nephron proximal tubules and their loss of function.

ChIP sequencing

A DNA sequencing analysis method for characterizing putative cis-regulatory DNA sequences bound by transcription factors and other DNA-binding proteins.

Lateral inhibition

A cell signalling process whereby a cell inhibits a neighbouring cell from activating a signalling event.

Lateral induction

A cell signalling process where a cell activates or allows a signal event to take place in a neighbouring cell.

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Schnell, J., Achieng, M. & Lindström, N.O. Principles of human and mouse nephron development. Nat Rev Nephrol 18, 628–642 (2022). https://doi.org/10.1038/s41581-022-00598-5

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