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 language | English (US) |
|---|---|
| Pages (from-to) | 825-840 |
| Number of pages | 16 |
| Journal | Journal of the American Society of Nephrology |
| Volume | 29 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2018 |
Funding
We thank all members of the McMahon laboratory for helpful discussion. We thank Dr. Rachel Steward and Dr. Melissa Wilson for their help providing tissue samples and with institutional review board approval processes. N.O.L., T.T., and A.P.M. planned experiments and analyzed data. N.O.L. and T.T. assembled the figures. N.O.L., T.T., R.K.P., J.G., and E.R. collected data. M.E.T. and B.G. provided embryonic and fetal kidneys. N.O.L. and A.P.M. wrote the manuscript, incorporating input from all authors. "We thank Hongsuda Tangmunarunkit and Laura Pearlman for their work integrating the imaging data into the Genito Urinary Development Molecular Anatomy Project (GUDMAP) database." Work in A.P.M.'s laboratory was supported by grants from the National Institutes of Health (DK107350, DK094526, DK110792) and the California Institute for Regenerative Medicine (LA1-06536). We thank all members of the McMahon laboratory for helpful discussion. We thank Dr. Rachel Steward and Dr. Melissa Wilson for their help providing tissue samples and with institutional review board approval processes. N.O.L., T.T., and A.P.M. planned experiments and analyzed data. N.O.L. and T.T. assembled the figures. N.O.L., T.T., R.K.P., J.G., and E.R. collected data. M.E.T. and B.G. provided embryonic and fetal kidneys. N.O.L. and A.P.M. wrote the manuscript, incorporating input from all authors. “We thank Hongsuda Tangmunarunkit and Laura Pearlman for their work integrating the imaging data into the GenitoUrinary Development Molecular Anatomy Project (GUDMAP) database.” Work in A.P.M.’s laboratory was supported by grants from the National Institutes of Health (DK107350, DK094526, DK110792) and the California Institute for Regenerative Medicine (LA1-06536).
ASJC Scopus subject areas
- General Medicine