title: WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland.
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.
authors.affiliation: Institute of Biology Valrose, iBV, University of Nice Sophia-Antipolis, 06108 Nice Cedex 2, France; INSERM UMR 1091, CNRS UMR 7277 Parc Valrose, 06108 Nice Cedex 2, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bandiera
authors.forename: Valerie P I
authors.initials: VP
authors.lastname: Vidal
authors.forename: Fariba Jian
authors.initials: FJ
authors.lastname: Motamedi
authors.forename: Michael
authors.initials: M
authors.lastname: Clarkson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sahut-Barnola
authors.forename: Alexander
authors.initials: A
authors.lastname: von Gise
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.forename: Antoine
authors.initials: A
authors.lastname: Martinez
authors.forename: Andreas
authors.initials: A
authors.lastname: Schedl
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002369:Castration; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000172:deficiency; D006066:Gonads / Q000166:cytology* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050991:GATA4 Transcription Factor; D012739:Gonadal Steroid Hormones; D051741:Kruppel-Like Transcription Factors; D025721:WT1 Proteins; D000071676:Zinc Finger Protein GLI1; C484171:Gata4 protein, mouse; C498520:Gli1 protein, mouse; C112923:Tcf21 protein, mouse