| First Author | Theis A | Year | 2021 |
| Journal | Development | Volume | 148 |
| Issue | 6 | PubMed ID | 33658226 |
| Mgi Jnum | J:307817 | Mgi Id | MGI:6725185 |
| Doi | 10.1242/dev.192401 | Citation | Theis A, et al. (2021) Groucho co-repressor proteins regulate beta cell development and proliferation by repressing Foxa1 in the developing mouse pancreas. Development 148(6):dev192401 |
| abstractText | 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 in vivo 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 beta cell development, and in the absence of Grg3 there is compensatory upregulation of Grg4 Grg3/4 double mutant mice have severe dysregulation of the pancreas gene program with ectopic expression of canonical liver genes and Foxa1, a master regulator of the liver program. Neurod1, an essential beta cell transcription factor and predicted target of Foxa1, becomes downregulated in Grg3/4 mutants, resulting in reduced beta cell proliferation, hyperglycemia, and early lethality. These findings uncover novel functions of GRG-mediated repression during pancreas development. |
