Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia

Scott Boyle, Andrew Misfeldt, Kelly J. Chandler, Karen K. Deal, E. Michelle Southard-Smith, Douglas P. Mortlock, H. Scott Baldwin, Mark de Caestecker

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

Classic tissue recombination and in vitro lineage tracing studies suggest that condensed metanephric mesenchyme (MM) gives rise to nephronic epithelium of the adult kidney. However, these studies do not distinguish between cap mesenchyme and pre-tubular aggregates comprising the condensed MM, nor do they establish whether these cells have self-renewing capacity. To address these questions, we generated Cited1-CreERT2 BAC transgenic mice, which express tamoxifen-regulated Cre recombinase exclusively in the cap mesenchyme. Fate mapping was performed by crossing these mice with the Rosa26RLacZ reporter line and evaluating the location and cellular characteristics of LacZ positive cells at different time points following tamoxifen injection. These studies confirmed expected results from previous in vitro analysis of MM cell fate, and provide in vivo evidence that the cap mesenchyme does not contribute to collecting duct epithelium in the adult. Furthermore, by exploiting the temporally regulated Cre recombinase, these studies show that nephronic epithelium arising at different stages of nephrogenesis has distinct spatial distribution in the adult kidney, and demonstrate for the first time that the cap mesenchyme includes a population of self-renewing epithelial progenitor cells.

Original languageEnglish
Pages (from-to)234-245
Number of pages12
JournalDevelopmental Biology
Volume313
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Cap mesenchyme
  • Cited1 BAC transgenic mice
  • Kidney development
  • Lineage tracing
  • Metanephric mesenchyme

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