title: Post-transcriptional mechanisms contribute to Etv2 repression during vascular development.
abstract: etv2 is an endothelial-specific ETS transcription factor that is essential for vascular differentiation and morphogenesis in vertebrates. While recent data suggest that Etv2 is dynamically regulated during vascular development, little is known about the mechanisms involved in this process. Here, we find that etv2 transcript and protein expression are highly dynamic during zebrafish vascular development, with both apparent during early somitogenesis and subsequently down-regulated as development proceeds. Inducible knockdown of Etv2 in zebrafish embryos prior to mid-somitogenesis stages, but not later, caused severe vascular defects, suggesting a specific role in early commitment of lateral mesoderm to the endothelial linage. Accordingly, Etv2-overexpressing cells showed an enhanced ability to commit to endothelial lineages in mosaic embryos. We further find that the etv2 3' untranslated region (UTR) is capable of repressing an endothelial autonomous transgene and contains binding sites for members of the let-7 family of microRNAs. Ectopic expression of let-7a could repress the etv2 3'UTR in sensor assays and was also able to block endogenous Etv2 protein expression, leading to concomitant reduction of endothelial genes. Finally, we observed that Etv2 protein levels persisted in maternal-zygotic dicer1 mutant embryos, suggesting that microRNAs contribute to its repression during vascular development. Taken together, our results suggest that etv2 acts during early development to specify endothelial lineages and is then down-regulated, in part through post-transcriptional repression by microRNAs, to allow normal vascular development.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: john2.moore@umassmed.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Moore
authors.forename: Sarah
authors.initials: S
authors.lastname: Sheppard-Tindell
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Shestopalov
authors.forename: Sayumi
authors.initials: S
authors.lastname: Yamazoe
authors.forename: James K
authors.initials: JK
authors.lastname: Chen
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C509408:Etv2 protein, zebrafish; D035683:MicroRNAs; D029961:Zebrafish Proteins
keywords: Angioblast; Endothelial; Etv2; Let-7; Post-transcriptional regulation; Zebrafish; microRNA
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