The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation
The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation
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DOI：
10.1101/gad.11.10.1253
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发表时间：
1997-05-15
影响因子：
10.5
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
McClatchey, AI;Saotome, I;Jacks, T
神经纤维瘤病II型（NF2）肿瘤抑制基因编码一种推定的细胞骨架相关蛋白，其缺失导致人类与NF2相关的许旺细胞肿瘤的发展。NF2蛋白Merlin属于将膜蛋白连接到细胞骨架的带4.1蛋白家族，并且被认为参与动态细胞骨架重组。然而，除了梅林家族的成员之外，人们对梅林的功能仍然知之甚少。为了分析Merlin在胚胎发生过程中的功能，并开发一个系统来详细研究Merlin的功能，我们已经破坏了小鼠Nf2基因在胚胎干细胞中的同源重组。大多数Nf2基因座突变的纯合子胚胎在胚胎第6.5和7.0天之间失败，表现出塌陷的胚外区域和没有组织的胚外外外胚层。胚胎继续发育，但不能启动原肠胚形成。这些观察结果得到了胚外谱系标记物表达模式和突变胚胎中中胚层标记物表达缺乏的支持。镶嵌研究表明，merlin功能不是细胞自主需要的中胚层，并支持的主张，merlin功能是必不可少的胚胎外结构在早期小鼠发育。
The neurofibromatosis type II (NF2) tumor suppressor encodes a putative cytoskeletal associated protein, the loss of which leads to the development of Schwann cell tumors associated with NF2 in humans. The NF2 protein merlin belongs to the band 4.1 family of proteins that link membrane proteins to the cytoskeleton and are thought to be involved in dynamic cytoskeletal reorganization. Beyond its membership in this family, however, the function of merlin remains poorly understood. In order to analyze the function of merlin during embryogenesis and to develop a system to study merlin function in detail, we have disrupted the mouse Nf2 gene by homologous recombination in embryonic stem cells. Most embryos homozygous for a mutation at the Nf2 locus fail between embryonic days 6.5 and 7.0, exhibiting a collapsed extraembryonic region and the absence of organized extraembryonic ectoderm. The embryo proper continues to develop, but fails to initiate gastrulation. These observations are supported by the expression patterns of markers of the extraembryonic lineage and the lack of expression of mesodermal markers in the mutant embryos. Mosaic studies demonstrate that merlin function is not required cell autonomously in mesoderm, and support the proposition that merlin function is essential for the development of extraembryonic structures during early mouse development.