The transcription factor Rreb1 regulates epithelial architecture and invasiveness in gastrulating mouse embryos

2020 ◽  
Author(s):  
Sophie M. Morgani ◽  
Jie Su ◽  
Jennifer Nichols ◽  
Joan Massagué ◽  
Anna-Katerina Hadjantonakis

AbstractRas-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor downstream of RAS signaling. Rreb1 has been implicated in cancer but little is known about its role in mammalian non-disease states. Here, we found that Rreb1 is essential for mouse embryonic development. Loss of Rreb1 led to a reduction in the expression of vasculogenesis factors, cardiovascular defects and embryonic lethality. During gastrulation, the absence of Rreb1 also resulted in the upregulation of cytoskeleton-associated genes, a change in the organization of F-ACTIN and adherens junctions within the pluripotent epiblast, and perturbed epithelial architecture characterized by irregular tissue folding and abnormal accumulations of cells. Moreover, Rreb1 mutant cells ectopically exited the epiblast epithelium through the underlying basement membrane, paralleling cell behaviors observed during metastasis. Thus, disentangling the function of Rreb1 in development could shed light on its role in cancer and other diseases involving loss of epithelial integrity.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sophie M Morgani ◽  
Jie Su ◽  
Jennifer Nichols ◽  
Joan Massagué ◽  
Anna-Katerina Hadjantonakis

Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. Rreb1 has been implicated in cancer and Noonan-like RASopathies. However, little is known about its role in mammalian non-disease states. Here, we show that Rreb1 is essential for mouse embryonic development. Loss of Rreb1 led to a reduction in the expression of vasculogenic factors, cardiovascular defects and embryonic lethality. During gastrulation, the absence of Rreb1 also resulted in the upregulation of cytoskeleton-associated genes, a change in the organization of F-ACTIN and adherens junctions within the pluripotent epiblast, and perturbed epithelial architecture. Moreover, Rreb1 mutant cells ectopically exited the epiblast epithelium through the underlying basement membrane, paralleling cell behaviors observed during metastasis. Thus, disentangling the function of Rreb1 in development should shed light on its role in cancer and other diseases involving loss of epithelial integrity.


Open Biology ◽  
2016 ◽  
Vol 6 (10) ◽  
pp. 160237
Author(s):  
David Sillam-Dussès ◽  
Robert Hanus ◽  
Michael Poulsen ◽  
Virginie Roy ◽  
Maryline Favier ◽  
...  

2020 ◽  
Author(s):  
Yanqiu Zhu ◽  
Huihui Wang ◽  
Wenjing Jia ◽  
Xiaoyan Wei ◽  
Zhikun Duan ◽  
...  

Abstract Background: The growth and development of wheat are seriously influenced by drought stress, and the research on drought resistance mechanism of wheat is very important. Dehydration responsive element binding protein (DREB) plays an important role in plant response to drought stress, but epigenetic regulation for gene expression of DREB transcription factor is less studied, especially the regulatory role of DNA methylation has not been reported.Results: In this research, DREB2, DREB6 and Wdreb2 were cloned from wheat in this study, their CDS sequence was composed of 732bp, 837bp or 1035bp, respectively, one 712bp intron was found in DREB6. Although AP2/EREBP domain of DREB2, DREB6 and Wdreb2 had 73.25% identity, they belong to different types of DREB transcription factor, and the expression of Wdreb2 was significantly higher, yet was the lowest in DREB2. Under drought stress, the expression of DREB2, DREB6 and Wdreb2 could be induced, but had different trends along with the increase of stress time, and their expression had tissue specificity, was obviously higher in leaf. Promoter of DREB2, DREB6 and Wdreb2 in leaf was further studied, some elements related to adverse stress were found, and the promoter of DREB2 and Wdreb2 was slightly methylated, but DREB6 promoter was mildly methylated. Compared with the control, the level of promoter methylation decreased in DREB2 and DREB6 as stressed for 2h, then increased along with the increase of stress time, which was opposite in Wdreb2 promoter, the status of promoter methylation also had significant change under drought stress. Further analysis showed that promoter methylation of DREB6 or Wdreb2 was negatively correlated with their expression, especially was significant in Wdreb2. Conclusions: DREB2, DREB6 and Wdreb2 might function differently in response to drought stress, and promoter methylation had more significant effects on gene expression of Wdreb2 and DREB6.


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