| Autor: |
Theis, Alexandra, Singer, Ruth A., Garofalo, Diana, Paul, Alexander, Narayana, Anila, Sussel, Lori |
| Předmět: |
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| Zdroj: |
Development (09501991); Mar2021, Vol. 148 Issue 6, p1-14, 14p |
| Abstrakt: |
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 β cell development, and in the absence of Grg3 there is compensatory upregulation of Grg4. Grg3/4 doublemutant 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 β cell transcription factor and predicted target of Foxa1, becomes downregulated in Grg3/4 mutants, resulting in reduced β cell proliferation, hyperglycemia, and early lethality. These findings uncover novel functions of GRG-mediated repression during pancreas development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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