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

Research output: Contribution to journalArticle

  • 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

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)5-18
Number of pages14
JournalDevelopmental Cell
Volume27
Issue number1
DOIs
Publication statusPublished - 14 Oct 2013

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.

    Research areas

  • 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

ID: 11027126