info:eu-repo/semantics/article
Rathke’s cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors
Fecha
2020-08Registro en:
Brinkmeier, Michelle L.; Bando, Hironori; Camarano, Adriana Carla; Fujio, Shingo; Yoshimoto, Koji; et al.; Rathke’s cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors; American Society for Clinical Investigation; Journal of Clinical Investigation; 140; 8; 8-2020; 4501-4515
0021-9738
CONICET Digital
CONICET
Autor
Brinkmeier, Michelle L.
Bando, Hironori
Camarano, Adriana Carla
Fujio, Shingo
Yoshimoto, Koji
Silva Junqueira de Souza, Flávio
Camper, Sally
Resumen
The transcription factor ISL1 is expressed in pituitary gland stem cells and the thyrotrope and gonadotrope lineages. Pituitary-specific Isl1 deletion causes hypopituitarism with increased stem cell apoptosis, reduced differentiation of thyrotropes and gonadotropes, and reduced body size. Conditional Isl1 deletion causes development of multiple Rathke’s cleft-like cysts, with 100% penetrance. Foxa1 and Foxj1 are abnormally expressed in the pituitary gland and associated with a ciliogenic gene-expression program in the cysts. We confirmed expression of FOXA1, FOXJ1, and stem cell markers in human Rathke’s cleft cyst tissue, but not craniopharyngiomas, which suggests these transcription factors are useful, pathological markers for diagnosis of Rathke’s cleft cysts. These studies support a model whereby expression of ISL1 in pituitary progenitors drives differentiation into thyrotropes and gonadotropes and without it, activation of FOXA1 and FOXJ1 permits development of an oral epithelial cell fate with mucinous cysts. This pituitary-specific Isl1 mouse knockout sheds light on the etiology of Rathke’s cleft cysts and the role of ISL1 in normal pituitary development.