Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary During Kidney Development

Dev Cell. 2017 May 22;41(4):349-365.e3. doi: 10.1016/j.devcel.2017.04.022.

Abstract

The kidney contains the functional units, the nephrons, surrounded by the renal interstitium. Previously we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of kidney development, descendant cells from these populations contribute exclusively to the main body of nephrons and renal interstitial tissues, respectively, indicating a lineage boundary between the nephron and renal interstitial compartments. Currently it is unclear how lineages are regulated during kidney organogenesis. We demonstrate that nephron progenitor cells lacking Pax2 fail to differentiate into nephron cells but can switch fates into renal interstitium-like cell types. These data suggest that Pax2 function maintains nephron progenitor cells by repressing a renal interstitial cell program. Thus, the lineage boundary between the nephron and renal interstitial compartments is maintained by the Pax2 activity in nephron progenitor cells during kidney organogenesis.

Keywords: FOXD1; PAX2; SIX2; cell fate; interstitium; kidney; lineage boundary; nephron; progenitor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Body Patterning* / genetics
  • Cell Transdifferentiation
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Homeodomain Proteins / metabolism
  • Mesoderm / cytology
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mice, Inbred C57BL
  • Nephrons / cytology*
  • Nephrons / embryology*
  • Nephrons / metabolism
  • Organogenesis / genetics
  • PAX2 Transcription Factor / metabolism*
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Stromal Cells / metabolism
  • Transcription Factors / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxd1 protein, mouse
  • Homeodomain Proteins
  • PAX2 Transcription Factor
  • Six2 protein, mouse
  • Transcription Factors