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The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos.

Published version
Peer-reviewed

Type

Article

Change log

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.

Description

Keywords

Rreb1, cardiovascular development, cell biology, development, developmental biology, epithelium, gastrulation, invasion, mouse, Actins, Adherens Junctions, Animals, Blood Vessels, DNA-Binding Proteins, Embryonic Development, Epithelial Cells, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Transcription Factors

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

10

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Wellcome Trust (110151/Z/15/Z)
Medical Research Council (MC_PC_17230)