Article: Role of a novel zebrafish nup98 during embryonic development
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- Publisher Website: 10.1016/j.exphem.2010.07.010
- Scopus: eid_2-s2.0-78649344144
- PMID: 20696206
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| Title | Role of a novel zebrafish nup98 during embryonic development | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Fung, TK1 Chung, MIS1 Liang, R1 Leung, AYH1 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/exphem | ||||||
| Citation | Experimental Hematology, 2010, v. 38 n. 11, p. 1014-1021.e2 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.exphem.2010.07.010 | ||||||
| Abstract | Objective: The nucleoporin NUP98 is a component of the nuclear pore complex that regulates nucleocytoplasmic trafficking. It has been characterized in acute myeloid leukemia as a fusion partner during chromosomal translocation. In this study, we identified a zebrafish nup98 gene and examined its role in embryonic development. Materials and Methods: Two expressed sequence tags with translated sequences homologous to human NUP98 were identified. The gene was cloned by polymerase chain reaction from complementary DNA of zebrafish embryos. Cellular functions of zebrafish NUP98 were investigated in HeLa cells. nup98 expression and developmental functions in zebrafish embryos were investigated by whole-mount in situ hybridization and morpholino knockdown. Results: Protein sequence of zebrafish nup98 shared 65% identity with its human homolog. Ectopic expression of zebrafish nup98 rescued the defective messenger RNA export due to human NUP98 knockdown in HeLa cells. In zebrafish embryos, nup98 was expressed diffusely in eyes and the developing brain since 18 hours postfertilization. Knockdown of nup98 with morpholino upregulated pu.1 expression by 39% ± 15% (p = 0.0153) and scl expression by 36% ± 7.6% (p = 0.0017). Expression of genes associated with erythropoiesis was unchanged. The morphants also developed intracranial hemorrhage at 48 hours postfertilization due to defective blood vessel development. Conclusions: A novel zebrafish nup98 was identified and it serves a role in nucleocytoplasmic trafficking similar to human NUP98. During development, it modulates hematopoietic stem cell and early myeloid development and maintains the integrity of cranial vasculature in the developing central nervous system. © 2010 ISEH - Society for Hematology and Stem Cells. | ||||||
| ISSN | 0301-472X 2011 Impact Factor: 2.905 2011 SCImago Journal Rankings: 0.440 | ||||||
| DOI | http://dx.doi.org/10.1016/j.exphem.2010.07.010 | ||||||
| ISI Accession Number ID | WOS:000284131500005
Funding Information: We thank the Confocal Microscopy Core Facility LKS Faculty of Medicine HKU and acknowledge the pcDNA3 mRFP plasmid from Dr Doug Golenbock from Addgene This work was supported by General Research Fund (HKU 769809M HKU 7520/06M) a small project fund from the University of Hong Kong (200807176190) and a fund from the Strategy Theme of Cancer Stem Cell LSK Faculty of Medicine HKU | ||||||
| References | References in Scopus | ||||||
| Grants | The roles of survivin in hematopoiesis, angiogenesis and tumorigenesis in a zebrafish knock-down and transgenic model The role of NUP98 in hematopoiesis in zebrafish and generation of zebrafish model for NUP98-HOXA9 overexpression Is aldehyde dehydrogenase a negative regulator of primitive hematopoiesis during embryonic development? |
| dc.contributor.author | Fung, TK | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chung, MIS | ||||||
| dc.contributor.author | Liang, R | ||||||
| dc.contributor.author | Leung, AYH | ||||||
| dc.date.accessioned | 2010-10-31T11:07:26Z | ||||||
| dc.date.available | 2010-10-31T11:07:26Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Objective: The nucleoporin NUP98 is a component of the nuclear pore complex that regulates nucleocytoplasmic trafficking. It has been characterized in acute myeloid leukemia as a fusion partner during chromosomal translocation. In this study, we identified a zebrafish nup98 gene and examined its role in embryonic development. Materials and Methods: Two expressed sequence tags with translated sequences homologous to human NUP98 were identified. The gene was cloned by polymerase chain reaction from complementary DNA of zebrafish embryos. Cellular functions of zebrafish NUP98 were investigated in HeLa cells. nup98 expression and developmental functions in zebrafish embryos were investigated by whole-mount in situ hybridization and morpholino knockdown. Results: Protein sequence of zebrafish nup98 shared 65% identity with its human homolog. Ectopic expression of zebrafish nup98 rescued the defective messenger RNA export due to human NUP98 knockdown in HeLa cells. In zebrafish embryos, nup98 was expressed diffusely in eyes and the developing brain since 18 hours postfertilization. Knockdown of nup98 with morpholino upregulated pu.1 expression by 39% ± 15% (p = 0.0153) and scl expression by 36% ± 7.6% (p = 0.0017). Expression of genes associated with erythropoiesis was unchanged. The morphants also developed intracranial hemorrhage at 48 hours postfertilization due to defective blood vessel development. Conclusions: A novel zebrafish nup98 was identified and it serves a role in nucleocytoplasmic trafficking similar to human NUP98. During development, it modulates hematopoietic stem cell and early myeloid development and maintains the integrity of cranial vasculature in the developing central nervous system. © 2010 ISEH - Society for Hematology and Stem Cells. | ||||||
| dc.description.grant | The roles of survivin in hematopoiesis, angiogenesis and tumorigenesis in a zebrafish knock-down and transgenic model | ||||||
| dc.description.grant | The role of NUP98 in hematopoiesis in zebrafish and generation of zebrafish model for NUP98-HOXA9 overexpression | ||||||
| dc.description.grant | Is aldehyde dehydrogenase a negative regulator of primitive hematopoiesis during embryonic development? | ||||||
| dc.description.grantcode | 82214 | ||||||
| dc.description.grantcode | 99222 | ||||||
| dc.description.grantcode | 100497 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Experimental Hematology, 2010, v. 38 n. 11, p. 1014-1021.e2 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.exphem.2010.07.010 | ||||||
| dc.identifier.citeulike | 7714800 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.exphem.2010.07.010 | ||||||
| dc.identifier.epage | 1021.e2 | ||||||
| dc.identifier.hkuros | 180358 | ||||||
| dc.identifier.isi | WOS:000284131500005
Funding Information: We thank the Confocal Microscopy Core Facility LKS Faculty of Medicine HKU and acknowledge the pcDNA3 mRFP plasmid from Dr Doug Golenbock from Addgene This work was supported by General Research Fund (HKU 769809M HKU 7520/06M) a small project fund from the University of Hong Kong (200807176190) and a fund from the Strategy Theme of Cancer Stem Cell LSK Faculty of Medicine HKU | ||||||
| dc.identifier.issn | 0301-472X 2011 Impact Factor: 2.905 2011 SCImago Journal Rankings: 0.440 | ||||||
| dc.identifier.issue | 11 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 20696206 | ||||||
| dc.identifier.scopus | eid_2-s2.0-78649344144 | ||||||
| dc.identifier.spage | 1014 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/125028 | ||||||
| dc.identifier.volume | 38 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/exphem | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Experimental Hematology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Amino Acid Sequence | ||||||
| dc.subject.mesh | Embryo, Nonmammalian - embryology - metabolism | ||||||
| dc.subject.mesh | Nuclear Pore Complex Proteins - genetics - metabolism - physiology | ||||||
| dc.subject.mesh | Zebrafish - embryology - genetics | ||||||
| dc.subject.mesh | Zebrafish Proteins - genetics - metabolism - physiology | ||||||
| dc.title | Role of a novel zebrafish nup98 during embryonic development | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine