Rathke’s cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors

Michelle L. Brinkmeier, Hironori Bando, Adriana C. Camarano, Shingo Fujio, Koji Yoshimoto, Flávio S.J. de Souza, Sally A. Camper

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)4501-4515
Number of pages15
JournalJournal of Clinical Investigation
Issue number8
Publication statusPublished - Aug 3 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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