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Rybp/DEDAF Is Required for Early Postimplantation and for Central Nervous System Development

机译：Rybp / DEDAF是早期植入后和中枢神经系统发育所必需的

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The Rybp/DEDAF protein has been implicated in both transcriptional regulation and apoptotic signaling, but its precise molecular function is unclear. To determine the physiological role of Rybp, we analyzed its expression during mouse development and generated mice carrying a targeted deletion of Rybp using homologous recombination in embryonic stem cells. Rybp was found to be broadly expressed during embryogenesis and was particularly abundant in extraembryonic tissues, including trophoblast giant cells. Consistent with this result, rybp homozygous null embryos exhibited lethality at the early postimplantation stage. At this time, Rybp was essential for survival of the embryo, for the establishment of functional extraembryonic structures, and for the execution of full decidualization. Through the use of a chimeric approach, the embryonic lethal phenotype was circumvented and a role for Rybp in central nervous system development was uncovered. Specifically, the presence of Rybp-deficient cells resulted in marked forebrain overgrowth and in localized regions of disrupted neural tube closure. Functions for Rybp in the brain also were supported by the finding of exencephaly in about 15% of rybp heterozygous mutant embryos, and by Rybp's distinct neural expression pattern. Together, these findings support critical roles for Rybp at multiple stages of mouse embryogenesis.
机译：Rybp / DEDAF蛋白已参与转录调控和凋亡信号转导，但其确切的分子功能尚不清楚。为了确定Rybp的生理作用，我们分析了其在小鼠发育过程中的表达，并通过在胚胎干细胞中使用同源重组产生了带有Rybp的靶向缺失的小鼠。发现Rybp在胚胎发生期间广泛表达，并且在胚外组织，包括滋养层巨细胞中特别丰富。与这个结果一致的是， rybp 纯合的无效胚在植入后的早期阶段表现出致死性。此时，Rybp对于胚胎的存活，功能性胚外结构的建立以及完全蜕膜化的执行至关重要。通过使用嵌合的方法，避免了胚胎致死表型，并且发现了Rybp在中枢神经系统发育中的作用。具体来说，Rybp缺陷细胞的存在导致明显的前脑过度生长和神经管闭合破坏的局部区域。 Rybp在大脑中的功能还受到大约15％的 rybp 杂合突变体胚胎中的能动性的发现以及Rybp独特的神经表达模式的支持。在一起，这些发现支持Rybp在小鼠胚胎发生的多个阶段的关键作用。

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