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非洲爪蟾早期胚胎发育过程中的差异基因表达图谱。

An atlas of differential gene expression during early Xenopus embryogenesis.

作者信息

Pollet Nicolas, Muncke Nadja, Verbeek Barbara, Li Yan, Fenger Ursula, Delius Hajo, Niehrs Christof

机构信息

Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

出版信息

Mech Dev. 2005 Mar;122(3):365-439. doi: 10.1016/j.mod.2004.11.009. Epub 2004 Dec 30.

Abstract

We have carried out a large-scale, semi-automated whole-mount in situ hybridization screen of 8369 cDNA clones in Xenopus laevis embryos. We confirm that differential gene expression is prevalent during embryogenesis since 24% of the clones are expressed non-ubiquitously and 8% are organ or cell type specific marker genes. Sequence analysis and clustering yielded 723 unique genes displaying a differential expression pattern. Of these, 18% were already described in Xenopus, 47% have homologs and 35% are lacking significant sequence similarity in databases. Many of them encode known developmental regulators. We classified 363 of the 723 genes for which a Gene Ontology annotation for molecular function could be attributed and found 'DNA binding' and 'enzyme' the most represented terms. The most common protein domains encoded in these embryonic, differentially expressed genes are the homeobox and RNA Recognition Motif (RRM). Fifty-nine putative orthologs of human disease genes, and 254 organ or cell specific marker genes were identified. Markers were found for nasal placode and archenteron roof, organs for which a specific marker was previously unavailable. Markers were also found for novel subdomains of various other organs. The tissues for which most markers were found are muscle and epidermis. Expression of cell cycle regulators fell in two classes, containing proliferation-promoting and anti-proliferative genes, respectively. We identified 66 new members of the BMP4, chromatin, endoplasmic reticulum, and karyopherin synexpression groups, thus providing a first glimpse of their probable cellular roles. Cluster analysis of tissues to measure tissue relatedness yielded some unorthodox affinities besides expectable lineage relationships. In conclusion, this study represents an atlas of gene expression patterns, which reveals embryonic regionalization, provides novel marker genes, and makes predictions about the functional role of unknown genes.

摘要

我们对非洲爪蟾胚胎中的8369个cDNA克隆进行了大规模的半自动全胚胎原位杂交筛选。我们证实,差异基因表达在胚胎发育过程中普遍存在,因为24%的克隆并非普遍表达,8%是器官或细胞类型特异性标记基因。序列分析和聚类产生了723个显示差异表达模式的独特基因。其中,18%已在非洲爪蟾中被描述,47%有同源物,35%在数据库中缺乏显著的序列相似性。它们中的许多编码已知的发育调节因子。我们对723个基因中的363个进行了分类,这些基因可归因于分子功能的基因本体注释,发现“DNA结合”和“酶”是最具代表性的术语。这些胚胎差异表达基因中编码的最常见蛋白质结构域是同源异型框和RNA识别基序(RRM)。鉴定出了59个人类疾病基因的推定直系同源物和254个器官或细胞特异性标记基因。发现了鼻基板和原肠顶的标记,此前这些器官没有特异性标记。还发现了各种其他器官新亚结构域的标记。发现标记最多的组织是肌肉和表皮。细胞周期调节因子的表达分为两类,分别包含促进增殖和抗增殖基因。我们鉴定出了BMP4、染色质、内质网和核转运蛋白共表达组的66个新成员,从而初步了解了它们可能的细胞作用。对组织进行聚类分析以测量组织相关性,除了预期的谱系关系外,还产生了一些非传统的亲缘关系。总之,这项研究代表了一个基因表达模式图谱,揭示了胚胎区域化,提供了新的标记基因,并对未知基因的功能作用进行了预测。

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