WT1 Maintains Adrenal-Gonadal Primordium Identity and Marks a Population of AGP-like Progenitors within the Adrenal Gland

Roberto Bandiera, Valerie P I Vidal, Fariba Jian Motamedi, Michael Clarkson, Isabelle Sahut-Barnola, Alexander von Gise, William T Pu, Peter Hohenstein, Antoine Martinez, Andreas Schedl

Research output: Contribution to journalArticlepeer-review

Abstract

Adrenal glands and gonads share a common primordium (AGP), but the molecular events driving differentiation are poorly understood. Here we demonstrate that the Wilms tumor suppressor WT1 is a key factor defining AGP identity by inhibiting the steroidogenic differentiation process. Indeed, ectopic expression of WT1 precludes differentiation into adrenocortical steroidogenic cells by locking them into a progenitor state. Chromatin immunoprecipitation experiments identify Tcf21 and Gli1 as direct targets of WT1. Moreover, cell lineage tracing analyses identify a long-living progenitor population within the adrenal gland, characterized by the expression of WT1, GATA4, GLI1, and TCF21, that can generate steroidogenic cells in vivo. Strikingly, gonadectomy dramatically activates these WT1(+) cells and leads to their differentiation into gonadal steroidogenic tissue. Thus, our data describe a mechanism of response to organ loss by recreating hormone-producing cells at a heterotopic site.
Original languageEnglish
Pages (from-to)5-18
Number of pages14
JournalDevelopmental Cell
Volume27
Issue number1
DOIs
Publication statusPublished - 14 Oct 2013

Keywords

  • Adrenal Glands/cytology
  • Adrenal Glands/metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Castration
  • Cell Differentiation
  • Cell Lineage
  • Embryonic Stem Cells
  • GATA4 Transcription Factor
  • Gonadal Steroid Hormones/deficiency
  • Gonads/cytology
  • Gonads/metabolism
  • Kruppel-Like Transcription Factors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • WT1 Proteins/genetics
  • WT1 Proteins/metabolism

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