Transcriptional dynamics of endodermal organ formation.
Although endodermal organs including the liver, pancreas, and intestine are of significant therapeutic interest, the mechanism by which the endoderm is divided into organ domains during embryogenesis is not well understood. To better understand this process, global gene expression profiling was performed on early endodermal organ domains. This global analysis was followed up by dynamic immunofluorescence analysis of key transcription factors, uncovering novel expression patterns as well as cell surface proteins that allow prospective isolation of specific endodermal organ domains. Additionally, a repressive interaction between Cdx2 and Sox2 was found to occur at the prospective stomach-intestine border, with the hepatic and pancreatic domains forming at this boundary, and Hlxb9 was revealed to have graded expression along the dorsal-ventral axis. These results contribute to understanding the mechanism of endodermal organogenesis and should assist efforts to replicate this process using pluripotent stem cells.
Sherwood
Richard I
RI
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Chen
Tzong-Yang Albert
TY
Melton
Douglas A
DA
D000818:Animals; D019521:Body Patterning; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004707:Endoderm / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D014157:Transcription Factors; C084059:Hb9 protein, mouse