Gomez Gustavo A, Veldman Matthew B, Zhao Yan, Burgess Shawn, Lin Shuo
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2009;4(3):e4994. doi: 10.1371/journal.pone.0004994. Epub 2009 Mar 24.
The transcription factor Etsrp is required for vasculogenesis and primitive myelopoiesis in zebrafish. When ectopically expressed, etsrp is sufficient to induce the expression of many vascular and myeloid genes in zebrafish. The mammalian homolog of etsrp, ER71/Etv2, is also essential for vascular and hematopoietic development. To identify genes downstream of etsrp, gain-of-function experiments were performed for etsrp in zebrafish embryos followed by transcription profile analysis by microarray. Subsequent in vivo expression studies resulted in the identification of fourteen genes with blood and/or vascular expression, six of these being completely novel. Regulation of these genes by etsrp was confirmed by ectopic induction in etsrp overexpressing embryos and decreased expression in etsrp deficient embryos. Additional functional analysis of two newly discovered genes, hapln1b and sh3gl3, demonstrates their importance in embryonic vascular development. The results described here identify a group of genes downstream of etsrp likely to be critical for vascular and/or myeloid development.
转录因子Etsrp是斑马鱼血管生成和原始髓系造血所必需的。当异位表达时,etsrp足以诱导斑马鱼中许多血管和髓系基因的表达。etsrp的哺乳动物同源物ER71/Etv2对血管和造血发育也至关重要。为了鉴定etsrp下游的基因,在斑马鱼胚胎中对etsrp进行了功能获得实验,随后通过微阵列进行转录谱分析。随后的体内表达研究鉴定出了14个具有血液和/或血管表达的基因,其中6个是全新的。etsrp对这些基因的调控通过在etsrp过表达胚胎中的异位诱导以及在etsrp缺陷胚胎中的表达降低得到证实。对两个新发现的基因hapln1b和sh3gl3的进一步功能分析表明它们在胚胎血管发育中的重要性。此处描述的结果鉴定出了一组etsrp下游的基因,它们可能对血管和/或髓系发育至关重要。