WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland.
Dev Cell
; 27(1): 5-18, 2013 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-24135228
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.
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Base de dados:
MEDLINE
Assunto principal:
Glândulas Suprarrenais
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Proteínas WT1
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Células-Tronco Embrionárias
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Gônadas
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article