Critical role of biklf in erythroid cell differentiation in zebrafish.
Hematopoietic cells arise from ventral mesoderm in different vertebrates, but the mechanisms through which various factors contribute to the hematopoietic processes, including erythrogenesis, remain incompletely understood. The Krüppel-like transcription factor Biklf is preferentially expressed in blood islands throughout zebrafish embryogenesis, marking the region of future erythropoiesis [1]. In this paper, we show that expression of biklf is significantly suppressed in the blood-less mutants vampire and m683 in which primitive hematopoiesis is impaired. Knockdown of biklf using morpholino-based antisense oligonucleotides (biklf-MO) led to a potent reduction in the number of circulating blood cells and deficiency in hemoglobin production. Consistently, we found that the expression of beta(e3)globin is strongly suppressed in biklf-MO-injected embryos, while gata1 expression is partly inhibited at the 10-somite stage. In addition, analysis of reporter constructs driven by the GATA1 and beta-globin promoters showed that Biklf can positively regulate both genes. These results indicate that Biklf is required for erythroid cell differentiation in zebrafish.
Kawahara
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A
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Dawid
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IB
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D005914:Globins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D005914:Globins; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C080774:erythroid Kruppel-like factor; C494691:gata1a protein, zebrafish; C418487:klf4 protein, zebrafish; C489367:tal1 protein, zebrafish