Date of Award


Document Type

Open Access Thesis


Biological Sciences

First Advisor

Shannon Davis


The pituitary gland is a critical organ that is necessary for many physiological processes, including growth, reproduction, and stress response. These vital processes are regulated through the secretion of pituitary hormones from specialized cell types. Pituitary hormone-producing cells arise from a common pool of pituitary progenitors in the developing Rathke’s pouch, and mutations that disrupt the formation and differentiation of pituitary progenitors often result in hypopituitarism, pituitary adenomas, or craniopharyngiomas. Thus, it is necessary to determine the mechanisms of pituitary development in order to understand the ways in which these congenital defects and tumors develop and disrupt pituitary function. Canonical WNT signaling through CTNNB1 (β-CATENIN) is known to regulate the formation of the POU1F1 lineage, which includes somatotropes, lactotropes, and thyrotropes. When β-catenin is deleted during the initial formation of pituitary progenitors, Pou1f1 is not transcribed, leading to the loss of the POU1F1 lineage. However, when β-catenin is deleted after lineage specification, there is no observable effect. Similarly, the generation of a β- catenin gain-of-function allele in early pituitary progenitors or stem cells results in the formation of craniopharyngiomas, while stimulating β-CATENIN in differentiated cell types has no effect. To date, previous studies have not determined the role of canonical WNT signaling in-between these two critical time points in pituitary organogenesis. PROP1 is a pituitary-specific transcription factor that is expressed starting at e10.5, after vi pituitary progenitor formation, and the peak of its expression occurs around e12.5, prior to lineage specification. We utilized the Prop1-cre to conduct both loss- and gain-offunction studies on β-CATENIN during this critical window in pituitary gland development. Our results demonstrate that pituitary progenitors remain sensitive to β- CATENIN at this time point. Deletion of β-catenin during this critical window resulted in loss of the POU1F1 lineage, as expected, as well as an increase in the expression of TBX19 (TPIT), with a subsequent increase in the corticotrope population. Stimulating β- CATENIN during this same time point resulted in the formation of nodules resembling those in adamantinomatous craniopharyngiomas (ACPs), along with complete disruption of cell cycle exit and pituitary lineage determination, loss of all hormone-secreting cell types, and a reversion to a more oral ectoderm-like state.