The transcription factor Rreb1 regulates epithelial architecture, invasiveness and vasculogenesis in early mouse embryos
- Memorial Sloan Kettering Cancer Center, United States
- University of Cambridge, United Kingdom
- Memorial Sloan-Kettering Cancer Center, United States
Abstract
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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE148514. Source data files for Figure 3 have been provided.
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A single-cell molecular map of mouse gastrulation and early organogenesis.ArrayExpress, Atlas: E-MTAB-6967; Smart-seq2 endothelial cells: E-MTAB-6970; Tal1−/− chimaeras: E-MTAB-7325; wild-type chimaeras: E-MTAB-7324.
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The emergent landscape of the mouse gut endoderm at single-cell resolutionGEO, GSE123046 (scRNA-seq), GSE123124.
Article and author information
Author details
Anna-Katerina Hadjantonakis
Funding
Wellcome Trust (110151/Z/15/Z)
- Sophie M Morgani
National Institutes of Health (R01HD094868,R01DK084391,P30CA008748)
- Anna-Katerina Hadjantonakis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimentation: Animal experimentation: All mice used in this study were maintained in accordance with the guidelines of the Memorial Sloan Kettering Cancer Center (MSKCC) Institutional Animal Care and Use Committee (IACUC) under protocol number 03-12-017 (PI Hadjantonakis).
Reviewing Editor
- Lilianna Solnica-Krezel, Washington University School of Medicine, United States
Publication history
- Received: November 11, 2020
- Accepted: April 16, 2021
- Accepted Manuscript published: April 30, 2021 (version 1)
- Version of Record published: May 18, 2021 (version 2)
- Version of Record updated: June 10, 2021 (version 3)
Copyright
© 2021, Morgani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The transcription factor Rreb1 regulates epithelial architecture, invasiveness and vasculogenesis in early mouse embryos
eLife 10:e64811.
https://doi.org/10.7554/eLife.64811
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