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

Abstract

Ras-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.