Molecular determinants of WNT9b responsiveness in nephron progenitor cells.

Published online

Journal Article

Primed nephron progenitor cells (NPCs) appear in metanephric mesenchyme by E11.5 and differentiate in response to the inductive WNT9b signal from the ureteric bud. However, the NPC WNT-receptor complex is unknown. We obtained M15 cells from E10.5 mesonephric mesenchyme and systematically analyzed components required for canonical WNT9b-responsiveness. When M15 cells were transfected with a β-catenin luciferase reporter plasmid, exposure to recombinant WNT9b resulted in minimal luciferase activity. We then analyzed mRNA-expression of WNT-pathway components and identified Fzd1-6 and Lrp6 transcripts but not Rspo1. When M15 cells were treated with recombinant RSPO1 the response to transfected WNT9b was augmented 4.8-fold. Co-transfection of M15 cells with Fzd5 (but no other Fzd family member) further increased the WNT9b signal to 16.8-fold and siRNA knockdown of Fzd5 reduced the signal by 52%. Knockdown of Lrp6 resulted in 60% WNT9b signal reduction. We confirmed Fzd5, Lrp6 and Rspo1 mRNA expression in CITED1(+) NPCs from E15.5 embryonic mouse kidney. Thus, while many WNT signaling-pathway components are present by E10.5, optimum responsiveness of E11.5 cap mesenchyme requires that NPCs acquire RSPO1, FZD5 and LRP6.

Full Text

Duke Authors

Cited Authors

  • Dickinson, KK; Hammond, LC; Karner, CM; Hastie, ND; Carroll, TJ; Goodyer, P

Published Date

  • 2019

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • e0215139 -

PubMed ID

  • 30978219

Pubmed Central ID

  • 30978219

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0215139

Language

  • eng

Conference Location

  • United States