Groucho Co-repressor Proteins Regulate β Cell Development and Proliferation by Repressing in the Developing Mouse Pancreas

Groucho-related genes (GRGs) are transcriptional co-repressors that are crucial for many developmental processes. Several essential pancreatic transcription factors are capable of interacting with GRGs; however, the role of GRG-mediated transcriptional repression in pancreas development is still not well understood. In this study, we used complex mouse genetics and transcriptomic analyses to determine that GRG3 is essential for β cell development, and in the absence of there is compensatory upregulation of double mutant mice have severe dysregulation of the pancreas gene program with ectopic expression of canonical liver genes and , a master regulator of the liver program. , an essential β cell transcription factor and predicted target of , becomes downregulated in mutants, resulting in reduced β cell proliferation, hyperglycemia, and early lethality. These findings uncover novel functions of GRG-mediated repression during pancreas development.