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转录因子 Rreb1 调节早期小鼠胚胎中的上皮结构、侵袭和血管生成。

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

机构信息

Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.

Wellcome Trust-Medical Research Council Centre for Stem Cell Research, University of Cambridge, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Cambridge, United Kingdom.

出版信息

Elife. 2021 Apr 30;10:e64811. doi: 10.7554/eLife.64811.

DOI:10.7554/eLife.64811
PMID:33929320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8131102/
Abstract

Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. 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 led to a reduction in the expression of vasculogenic factors, cardiovascular defects, and embryonic lethality. During gastrulation, the absence of 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, 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.

摘要

Ras 响应元件结合蛋白 1（Rreb1）是一种锌指转录因子，作用于 RAS 信号下游。它与癌症和类似诺南的 RAS 病有关。然而，人们对其在哺乳动物非疾病状态下的作用知之甚少。在这里，我们表明 Rreb1 对小鼠胚胎发育至关重要。缺失 导致血管生成因子的表达减少、心血管缺陷和胚胎致死。在原肠胚形成过程中， 缺失也导致细胞骨架相关基因的上调、多能内胚层中 F-肌动蛋白和黏着连接的结构改变以及上皮结构的紊乱。此外， 突变细胞通过下伏的基膜异位离开内胚层上皮，类似于转移过程中观察到的细胞行为。因此，阐明 Rreb1 在发育中的功能应该揭示其在涉及上皮完整性丧失的癌症和其他疾病中的作用。

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