Conserved and divergent molecular and anatomic features of human and mouse nephron patterning

Nils O. Lindström, Tracy Tran, Jinjin Guo, Elisabeth Rutledge, Riana K. Parvez, Matthew E. Thornton, Brendan Grubbs, Jill A. McMahon, Andrew P. McMahon*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal-distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover,we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge - critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and ratmodels that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.

Original languageEnglish (US)
Pages (from-to)825-840
Number of pages16
JournalJournal of the American Society of Nephrology
Volume29
Issue number3
DOIs
StatePublished - Mar 2018

    Fingerprint

ASJC Scopus subject areas

  • Nephrology

Cite this

Lindström, N. O., Tran, T., Guo, J., Rutledge, E., Parvez, R. K., Thornton, M. E., Grubbs, B., McMahon, J. A., & McMahon, A. P. (2018). Conserved and divergent molecular and anatomic features of human and mouse nephron patterning. Journal of the American Society of Nephrology, 29(3), 825-840. https://doi.org/10.1681/ASN.2017091036