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首页> 外文期刊>Current Biology: CB >Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm specification cascade
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Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm specification cascade

机译:斑马鱼pou5f1 / pou2,哺乳动物Oct4的同源物,在内胚层规格级联中起作用

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摘要

pou5f1, also known as 004, is required to establish the pluripotent cell population necessary for embryogenesis in mouse [1]. Additional roles during development, including endoderm formation, have been proposed [2, 3]. In zebrafish, the zygotic pou5f1/pou2 mutant spiel ohne grenzen (spg) [4-6] shows neural plate patterning defects and reduced endoderm at the tailbud stage [7]. To investigate the function of maternal and early zygotic pou5f1 expression, we rescued zygotic spg(m793) mutants by injecting pou5f1 mRNA at the one-cell stage and raised them into fertile homozygous spg,,93 adults that mate to produce maternal-zygotic spg (MZspg) mutant embryos. Although neurectoderm, mesoderm, and germ cells develop in MZspg mutants, gastrulation is delayed and proceeds abnormally. Further, MZspg mutants do not maintain expression of sox32/casanova, express little or no sox17, and fail to develop endodermal tissue. Constitutively active Nodal receptor TARAM-A or sox32 overexpression induces ubiquitous sox17 expression in wild-type embryos [8-10], but not in MZspg mutants. Overexpression of a Pou5f1-VP16 activator fusion protein can rescue gastrulation and endodermal tissues in MZspg mutants. We propose that pou5f1 plays an activating role in zebrafish endodermal development, where it maintains sox32 expression during gastrulation and acts with sox32 to induce sox17 expression in endodermal precursor cells.
机译:pou5f1,也称为004,是建立小鼠胚胎发生所必需的多能细胞群所必需的[1]。已经提出了在发育过程中的其他作用,包括内胚层的形成[2,3]。在斑马鱼中,合子性pou5f1 / pou2突变体spiel ohne grenzen(spg)[4-6]在尾巴阶段显示出神经板构图缺陷和内胚层减少[7]。为了研究母体和早期合子pou5f1表达的功能,我们通过在单细胞阶段注入pou5f1 mRNA并将其培养为可育的纯合子spg来拯救合子spg(m793)突变体,93个成年后会产生母体-合子spg( MZspg)突变体胚胎。尽管在MZspg突变体中会出现中胚层,中胚层和生殖细胞,但胃形成会延迟并异常进行。此外,MZspg突变体不维持sox32 / casanova的表达,很少表达或不表达sox17,并且不能发育内胚层组织。组成型活性的Nodal受体TARAM-A或sox32过表达诱导野生型胚胎中普遍存在的sox17表达[8-10],但在MZspg突变体中不诱导。 Pou5f1-VP16激活剂融合蛋白​​的过表达可以挽救MZspg突变体中的胃形成和内皮组织。我们建议pou5f1在斑马鱼内胚层发育中起激活作用,在那里它在胃形成器官期间维持sox32的表达,并与sox32一起作用以诱导内胚层前体细胞中sox17的表达。

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