Abstract
BackgroundThe embryonic definitive endoderm (DE) gives rise to organs of the gastrointestinal and respiratory tract including the liver, pancreas and epithelia of the lung and colon. Understanding how DE progenitor cells generate these tissues is critical to understanding the cause of visceral organ disorders and cancers, and will ultimately lead to novel therapies including tissue and organ regeneration. However, investigation into the molecular mechanisms of DE differentiation has been hindered by the lack of early DE-specific markers.ResultsWe describe the identification of novel as well as known genes that are expressed in DE using Serial Analysis of Gene Expression (SAGE). We generated and analyzed three longSAGE libraries from early DE of murine embryos: early whole definitive endoderm (0–6 somite stage), foregut (8–12 somite stage), and hindgut (8–12 somite stage). A list of candidate genes enriched for expression in endoderm was compiled through comparisons within these three endoderm libraries and against 133 mouse longSAGE libraries generated by the Mouse Atlas of Gene Expression Project encompassing multiple embryonic tissues and stages. Using whole mount in situ hybridization, we confirmed that 22/32 (69%) genes showed previously uncharacterized expression in the DE. Importantly, two genes identified, Pyy and 5730521E12Rik, showed exclusive DE expression at early stages of endoderm patterning.ConclusionThe high efficiency of this endoderm screen indicates that our approach can be successfully used to analyze and validate the vast amount of data obtained by the Mouse Atlas of Gene Expression Project. Importantly, these novel early endoderm-expressing genes will be valuable for further investigation into the molecular mechanisms that regulate endoderm development.
Highlights
The embryonic definitive endoderm (DE) gives rise to organs of the gastrointestinal and respiratory tract including the liver, pancreas and epithelia of the lung and colon
A list of candidate genes enriched for expression in endoderm was compiled through comparisons within these three endoderm libraries and against 133 mouse longSAGE libraries representing multiple embryonic stages and tissues generated by the Mouse Atlas of Gene Expression Project [32,33]
By examining the expression patterns of our original list of 45 tag-sequences in 133 longSAGE libraries generated by the Mouse Atlas Project, we discovered 9 genes that exhibited high tissue-specificity since they were present in only a few libraries (Figure 5)
Summary
The embryonic definitive endoderm (DE) gives rise to organs of the gastrointestinal and respiratory tract including the liver, pancreas and epithelia of the lung and colon. The DE gives rise to the major cell types of many internal organs, including the thyroid, thymus, lung, stomach, liver, pancreas, intestine and bladder. Most of these organs have secretory and/or absorptive functions and play important roles in controlling body metabolism. Interest in the endoderm has intensified recently because processes that govern early development of DE-derived tissues may be recapitulated during stem cell differentiation [4,5], which could provide future therapies for diseased adult organs. Understanding how DEderived organs are specified, differentiate, proliferate, and undergo morphogenesis is key to understanding visceral organ disorders and tissue regeneration
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