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 (1)

1 IBV - Institut de Biologie Valrose

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.

Domaines: Biologie du développement

Roberto Bandiera, Valerie P I Vidal, Fariba Jian Motamedi, Michael Clarkson, Isabelle Sahut-Barnola, et al.. WT1 Maintains Adrenal-Gonadal Primordium Identity and Marks a Population of AGP-like Progenitors within the Adrenal Gland.. Developmental Cell, 2013, 27 (1), pp.5-18. ⟨10.1016/j.devcel.2013.09.003⟩. ⟨hal-00875587⟩