Gene expression in pharyngeal arch 1 during human embryonic development
Gene expression in pharyngeal arch 1 during human embryonic development
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DOI：
10.1093/hmg/ddi083
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Lovett, M
中科院分区：
文献类型：
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作者：
Cai, JL;Ash, D;Lovett, M
颅面畸形是人类最常见的出生缺陷之一，但人们对控制这些重要发育过程的人类基因知之甚少。为了鉴定相关基因，我们分析了人咽弓1（PA 1）的转录谱，PA 1是一种发育成腭和颌的保守胚胎结构。使用显微解剖的正常人类颅面结构，我们构建了12个SAGE（基因表达系列分析）库并对606532个标签进行了测序。我们还对25个颅面靶点进行了Affyssin微阵列分析。我们的数据显示，不仅基因“富集”或差异表达的PA 1在第四和第五周的人类发展，但也有6927个新发现的基因在人类PA 1中表达。这些基因中的许多参与生物合成过程，并具有结合功能和催化活性。我们比较了人类基因与小鼠同源基因的表达谱，以寻找对人类颅面发育更特异的基因，发现766个基因在人类PA 1中表达，但在小鼠PA 1中没有表达。我们还鉴定了1408个在小鼠和人类PA 1中表达的基因，这些基因可能有助于建立人类条件的小鼠模型。我们证实了一些人PA 1的表达模式在小鼠胚胎样品的整体原位杂交和实时RT-PCR的保守性。这种全面的表达分析方法可以深入了解颅面区域的早期发育，并为发育结构和候选基因提供标记，包括SET和CCT 3，用于口面裂和小颌畸形等疾病。
Craniofacial abnormalities are one of the most common birth defects in humans, but little is known about the human genes that control these important developmental processes. To identify relevant genes, we analyzed transcription profiles of human pharyngeal arch 1 (PA1), a conserved embryonic structure that develops into the palate and jaw. Using microdissected, normal human craniofacial structures, we constructed 12 SAGE (serial analysis of gene expression) libraries and sequenced 606 532 tags. We also performed Affymetrix microarray analysis on 25 craniofacial targets. Our data revealed not only genes 'enriched' or differentially expressed in PA1 during fourth and fifth week of human development, but also 6927 genes newly identified to be expressed in human PA1. Many of these genes are involved in biosynthetic processes and have binding function and catalytic activity. We compared expression profiles of human genes with those of mouse homologs to look for genes more specific to human craniofacial development and found 766 genes expressed in human PA1, but not in mouse PA1. We also identified 1408 genes that were expressed in mouse as well as human PA1 and could be useful in creating mouse models for human conditions. We confirmed conservation of some human PA1 expression patterns in mouse embryonic samples with whole mount in situ hybridization and real-time RT-PCR. This comprehensive approach to expression profiling gives insights into the early development of the craniofacial region and provides markers for developmental structures and candidate genes, including SET and CCT3, for diseases such as orofacial clefting and micrognathia.