Date of Award
12-1-2019
Degree Name
Doctor of Philosophy
Department
Molecular, Cellular, and Systemic Physiology
First Advisor
Ellsworth, Buffy
Abstract
The differentiation of growth hormone producing somatotropes in the pituitary gland is dependent upon signaling and transcription factors produced both within and outside the gland. In order to better understand this fundamental process, we have focused on investigating the contribution of forkhead factors FOXO1 and FOXO3. We sought to elucidate whether FOXO1 is sufficient to drive somatotrope differentiation in an over-expression mouse model, identify potential functional redundancy between closely related forkhead family members, and to specify the genetic targets of FOXO1 binding in the pituitary gland. Using a combination of mouse models and molecular techniques we have established a role for Foxo1 in early embryonic development, generated a somatotrope-specific FOXO1 binding enrichment library, revealed functional redundancy between FOXO1 and FOXO3 in the pituitary gland, and discovered a novel protein-protein interaction with YBX1. These results demonstrate FOXO factors are important for pituitary gland formation and function during both pre- and postnatal periods.
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