The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos.
The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos.
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DOI：
10.7554/elife.64811
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发表时间：
2021-04-30
期刊：
影响因子：
7.7
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Morgani SM;Su J;Nichols J;Massagué J;Hadjantonakis AK
Ras反应元件结合蛋白1（Rreb 1）是一种锌指转录因子，作用于RAS信号的下游。Rreb 1与癌症和努南样RASopathies有关。然而，很少有人知道它在哺乳动物的非疾病状态的作用。在这里，我们表明Rreb 1是小鼠胚胎发育所必需的。Rreb 1的缺失导致血管生成因子表达减少、心血管缺陷和胚胎死亡。在原肠胚形成过程中，Rreb 1的缺乏也导致了细胞因子相关基因的上调，多能性外胚层内F-ACTIN和粘附连接组织的变化，以及上皮结构的紊乱。此外，Rreb 1突变细胞异位退出上胚层上皮细胞通过下面的基底膜，平行转移过程中观察到的细胞行为。因此，解开Rreb 1在发育中的功能应该有助于阐明其在癌症和其他涉及上皮完整性丧失的疾病中的作用。
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.