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Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend
Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend
Theses and Dissertations
TGIF1 belongs to the superfamily of homeodomain proteins, which regulate a wide variety of biological functions, including cell stemness and specification of cell fate during early development. Perhaps surprisingly, we found that enforced expression in pancreatic progenitor cells during embryogenesis resulted in severe diabetes, hinting at the possibility that TGIF1 might regulate pancreas development. Subsequent genetic experiments targeting β-cells showed that TGIF1 affected β-cell function and homeostasis. Transcriptomic analysis revealed that TGIF1 expression inhibits the expression of essential components of UPR signaling, underscoring a potential mechanism in which TGIF1 disrupts protein folding and secretion. Congruently, TGIF1 expression led to a …