Premature Expression of Foxo1 Results in Pituitary Hypoplasia and Normal Timing of Somatotrope Differentiation

Presentation Number: SAT 438
Date of Presentation: April 1st, 2017

Caitlin Stallings*1 and Buffy Sue Ellsworth2
1Southern Illinois University, Carbondale, IL, 2Southern Illinois University Carbondale, Carbondale, IL

Abstract

Growth hormone is a marker of differentiated somatotropes and is first detected in mouse anterior pituitary gland tissue at approximately e16.5 by immunohistochemistry (IHC). The forkhead transcription factor, FOXO1, is first present in the nuclei of mouse pituitary cells at embryonic day (e)14.5. Deletion of Foxo1 in the pituitary gland results in delayed somatotrope differentiation. Based on these studies we hypothesized that constitutively active FOXO1 would cause premature somatotrope differentiation. In order to further understand the role of Foxo1 in the developing pituitary gland, a constitutively active form of FOXO1 (CA-FOXO1) was prematurely expressed in the pituitary gland by e10.5 (1). CA-FOXO1 animals present with a hypoplastic and occasionally dysmorphic pituitary gland that is positive for the HA tagged FOXO1 recombinant protein at e10.5. The mutation is perinatal lethal as no CA-FOXO1 pups are found alive after birth. A proliferation assay revealed no difference between CA-FOXO1 animals and controls indicating the hypoplastic pituitary gland is not due to a lack of cellular expansion at e10.5. It is possible the hypoplasia and especially the dysmorphia observed are the result of fewer cells being induced from the oral ectoderm to form Rathke’s pouch because of altered interaction of oral ectoderm with signaling factors during development. Interestingly, GH is not detected at e15.5 in CA-FOXO1 animals. Therefore, premature expression of Foxo1 does not cause early somatotrope differentiation in this model.

 

Nothing to Disclose: CS, BSE