Characterization of embryonic globin genes of the zebrafish

Brownlie, Alison; Hersey, Candace; Oates, Andrew C.; Paw, Barry H.; Falick, Arnold M.; Witkowska, H. Ewa; Flint, Jonathan; Higgs, Deborah; Jessen, Jason R.; Bahary, Nathan; Zhu, Min; Lin, Shuo; Zon, Leonard I.

doi:10.1016/s0012-1606(02)00041-6

Cited by 147 publications

(135 citation statements)

References 49 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…The primers for RT-PCR analysis of adult and embryonic gene expression have been described (30,31); the primers for cd41 were described in ref. 7.…”

Section: Methodsmentioning

confidence: 99%

Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved

Soza‐Ried

Hess

Netuschil

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

109

View full text Add to dashboard Cite

The transcription factor c-myb has emerged as one of the key regulators of vertebrate hematopoiesis. In mice, it is dispensable for primitive stages of blood cell development but essentially required for definitive hematopoiesis. Using a conditional knock-out strategy, recent studies have indicated that c-myb is required for self-renewal of mouse hematopoietic stem cells. Here, we describe and characterize the c-myb mutant in a lower vertebrate, the zebrafish Danio rerio . The recessive loss-of-function allele of c-myb ( c-myb t25127 ) was identified in a collection of N -ethyl- N -nitrosourea (ENU)-induced mutants exhibiting a failure of thymopoiesis. The sequence of the mutant allele predicts a missense mutation (I181N) in the middle of the DNA recognition helix of repeat 3 of the highly conserved DNA binding domain. In keeping with the findings in the mouse, primitive hematopoiesis is not affected in the c-myb mutant fish. By contrast, definitive hematopoiesis fails, resulting in the loss of all blood cells by day 20 of development. Thus, the mutant fish lack lymphocytes and other white and red blood cells; nonetheless, they survive for 2–3 mo but show stunted growth. Because the mutant fish survive into early adulthood, it was possible to directly show that their definitive hematopoiesis is permanently extinguished. Our results, therefore, suggest that the key role of c-myb in definitive hematopoiesis is similar to that in mammals and must have become established early in vertebrate evolution.

show abstract

“…The primers for RT-PCR analysis of adult and embryonic gene expression have been described (30,31); the primers for cd41 were described in ref. 7.…”

Section: Methodsmentioning

confidence: 99%

Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved

Soza‐Ried

Hess

Netuschil

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

109

View full text Add to dashboard Cite

show abstract

“…In addition, CNVs have also been associated with human disease phenotypes including neurological disorders (12), early onset obesity (13), and some forms of cancer (14). Although a few zebrafish CNVs have been studied previously [e.g., mannose binding lectin (15) and globin (16) genes], no comprehensive genome-wide assessment for zebrafish CNVs has yet been reported. We have conducted an assessment revealing an unprecedented high level of copy number polymorphisms distributed throughout the genome, with extensive within-(intra-) and between-(inter-) strain variation.…”

mentioning

confidence: 99%

Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis

Brown

Dobrinski

Lee

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNV elements exhibited strain specificity, with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen's large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and substructure of these commonly used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype and, if not properly addressed, such extensive levels of germ-line variation and population substructure in this commonly used model organism can potentially confound studies intended for translation to human diseases.

show abstract

“…To test this hypothesis, we examined the expression of various molecular markers for definitive hematopoiesis by whole-mount in situ hybridization. The expression of an erythroid marker hemoglobin alpha embryonic-1 (hbae1) [32] was markedly reduced in Ddx46 hi2137/hi2137 mutants at 3 dpf (Fig. 7A, B).…”

Section: Ddx46mentioning

confidence: 99%

“…In the course of the phenotypic analyses of Ddx46 hi2137/ hi2137 mutants, we also found that the expression of hematopoietic markers was downregulated in the mutants. At 22 hours postfertilization (hpf), the expression of the primitive hematopoietic markers tal1, LIM domain only 2 (lmo2) [31], gata1a, hemoglobin beta embryonic-3 (hbbe3) [32], and myeloid-specific peroxidase (mpx) [33] was normal in Ddx46 hi2137/ hi2137 mutants ( Fig. 1A-J).…”

Section: Ddx46mentioning

confidence: 99%

Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish

Hirabayashi

Hozumi

Higashijima

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. Here, we show that zebrafish Ddx46, encoding a DEAD-box RNA helicase, is expressed in HSCs of the caudal hematopoietic tissue (CHT). The number of HSCs expressing the molecular markers cmyb or T-cell acute lymphocytic leukemia 1 (tal1) was markedly reduced in Ddx46 mutants. However, massive cell death of HSCs was not detected, and proliferation of HSCs was normal in the CHT of the mutants at 48 h postfertilization. We found that myelopoiesis occurred, but erythropoiesis and lymphopoiesis were suppressed, in Ddx46 mutants. Consistent with these results, the expression of spi1, encoding a regulator of myeloid development, was maintained, but the expression of gata1a, encoding a regulator of erythrocyte development, was downregulated in the mutants. Taken together, our results provide the first genetic evidence that zebrafish Ddx46 is required for the multilineage differentiation of HSCs during development, through the regulation of specific gene expressions.

show abstract

Characterization of embryonic globin genes of the zebrafish

Cited by 147 publications

References 49 publications

Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved

Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved

Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis

Ddx46 Is Required for Multi-Lineage Differentiation of Hematopoietic Stem Cells in Zebrafish

Contact Info

Product

Resources

About