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对非洲爪蟾肠道的研究揭示了从胚胎到成年脊椎动物肠道适应的生物学途径。

Studies on Xenopus laevis intestine reveal biological pathways underlying vertebrate gut adaptation from embryo to adult.

机构信息

Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr, Bethesda, MD 20892, USA.

出版信息

Genome Biol. 2010;11(5):R55. doi: 10.1186/gb-2010-11-5-r55. Epub 2010 May 19.

Abstract

BACKGROUND

To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation.

RESULTS

The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis, respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Additionally, we identified larval/embryo- and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes.

CONCLUSIONS

This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications.

摘要

背景

为了适应不断变化的饮食环境,在脊椎动物的发育过程中,从胚胎到成年,消化道会广泛重塑。非洲爪蟾的变态发育是研究哺乳动物胃肠道发育的理想模型系统,用于确定肠道发育和成熟所必需的基因和信号程序。

结果

变态中的肠道可以分为四个不同的发育时间点,并使用非洲爪蟾微阵列进行了分析。由于发育信号程序在很大程度上保守且与哺乳动物基因同源,因此注释和生物信息学分析基于人类直系同源物。表达模式的聚类揭示了涉及凋亡和增殖等基本细胞过程的共表达基因。两个最大的基因簇分别在变态的高峰期有表达高峰和低谷。在此期间调节的新保守基因本体类别包括转录活性、信号转导和代谢过程。此外,我们还鉴定了幼虫/胚胎和成年特异性基因。详细分析显示了 17 个幼虫特异性基因,它们可能代表人类结肠癌症的分子标志物,而许多成年特异性基因与饮食酶有关。

结论

这项全面的发育表达研究提供了肠道重塑和成熟在胚胎后发育过程中的第一个详细分子描述,这应该有助于提高我们对肠道器官发生和人类疾病的理解。这项研究对我们理解发育和组织更新过程中的分子调控动态有重要贡献,这对于未来的基础和临床研究以及药物应用都很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b8e/2898076/1bd1b8cb3c8a/gb-2010-11-5-r55-1.jpg

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