| Experiment Id | GSE149891 | Name | Transcriptomic analyses of embryonic pancreata from pancreas-specific Groucho mutants |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-02-09 |
| description | A large number of studies have identified and characterized the many transcription factors and cofactors that regulate pancreas organogenesis. Groucho-related genes/Transducin-like Enhancer of Split (Grgs/TLEs) are one such family of cofactors that act as transcriptional co-repressors and are critical 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 only partially characterized. In this study, we used phenotypic 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. In Grg3/4 double mutants, mice have severe dysregulation of the pancreas gene program with ectopic expression of 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 a loss of beta cell proliferation, hyperglycemia, and early lethality. These findings uncover a novel function of GRG-mediated repression in pancreas development. e18.5 pancreas RNA-seq from Pdx1:Cre, Pdx1:Cre; Grg and Pdx1:Cre; Grg3/4 embryos (n=3 for each genotype) |
