title: Zebrafish ETV7 regulates red blood cell development through the cholesterol synthesis pathway.
abstract: ETV7 is a human oncoprotein that cooperates with Eμ-MYC to promote pre-B-cell leukemia in mice. It is normally expressed in the bone marrow and fetal liver and is upregulated in primary leukemia, suggesting that it is involved in proper hematopoiesis and leukemogenesis. ETV7 has been deleted in most rodents, but is conserved in all other vertebrates, including the zebrafish, Danio rerio. In this report, we characterize the function of the zebrafish etv7 gene during erythropoiesis. Our results demonstrate that etv7 regulates the expression of the zebrafish lanosterol synthase (lss) gene, an essential gene in the cholesterol synthesis pathway. Furthermore, morpholino knockdown of etv7 leads to loss of hemoglobin-containing red blood cells, a phenotype that can be rescued by injection of exogenous cholesterol. We conclude that etv7 is essential for normal red blood cell development through regulation of the lss gene and the cholesterol synthesis pathway.
authors.affiliation: St Jude Children's Research Hospital, Department of Genetics, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Quintana
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Picchione
authors.forename: Ramon I
authors.initials: RI
authors.lastname: Klein Geltink
authors.forename: Michael R
authors.initials: MR
authors.lastname: Taylor
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000096:biosynthesis*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D051379:Mice; D060172:Morpholinos / Q000494:pharmacology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism
chemical_list: C409823:ETV7 protein, human; C000593353:ETV7 protein, zebrafish; D050982:GATA1 Transcription Factor; D006454:Hemoglobins; D060172:Morpholinos; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D055544:beta-Globins; D002784:Cholesterol
keywords: Cholesterol; Oncogene; Red blood cell; etv7