title: Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue.
abstract: Cell fate decisions are integral to zonation and remodeling of the adrenal cortex. Animal models exhibiting ectopic differentiation of gonadal-like cells in the adrenal cortex can shed light on the molecular mechanisms regulating steroidogenic cell fate. In one such model, prepubertal gonadectomy (GDX) of mice triggers the formation of adrenocortical neoplasms that resemble luteinized ovarian stroma. Transcriptomic analysis and genome-wide DNA methylation mapping have identified genetic and epigenetic markers of GDX-induced adrenocortical neoplasia. Members of the GATA transcription factor family have emerged as key regulators of cell fate in this model. Expression of Gata4 is pivotal for the accumulation of gonadal-like cells in the adrenal glands of gonadectomized mice, whereas expression of Gata6 limits the spontaneous and GDX-induced differentiation of gonadal-like cells in the adrenal cortex. Additionally, Gata6 is essential for proper development of the adrenal X-zone, a layer analogous to the fetal zone of the human adrenal cortex. The relevance of these observations to developmental signaling pathways in the adrenal cortex, to other animal models of altered adrenocortical cell fate, and to human diseases is discussed.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Hochschule Mannheim - University of Applied Sciences, Mannheim 68163, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Röhrig
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki 00290, Finland.
authors.forename: Marjut
authors.initials: M
authors.lastname: Pihlajoki
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Hochschule Mannheim - University of Applied Sciences, Mannheim 68163, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Ziegler
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Cochran
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki 00290, Finland.
authors.forename: Anja
authors.initials: A
authors.lastname: Schrade
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA.
authors.forename: Maximiliaan
authors.initials: M
authors.lastname: Schillebeeckx
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA.
authors.forename: Robi D
authors.initials: RD
authors.lastname: Mitra
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki 00290, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA. Electronic address: wilson_d@wustl.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology*; D000306:Adrenal Cortex Neoplasms / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D006066:Gonads / Q000166:cytology*; D006801:Humans; D013234:Stem Cells / Q000166:cytology*
keywords: Adrenal cortex; Endocrine tumor; Ferret; Gonadotropin