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PMID:21228005

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Citation

Du, L, Xu, J, Li, X, Ma, N, Liu, Y, Peng, J, Osato, M, Zhang, W and Wen, Z (2011) Rumba and Haus3 are essential factors for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis. Development 138:619-29

Abstract

The hallmark of vertebrate definitive hematopoiesis is the establishment of the hematopoietic stem/progenitor cell (HSPC) pool during embryogenesis. This process involves a defined ontogenic switching of HSPCs in successive hematopoietic compartments and is evolutionarily conserved from teleost fish to human. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), from which they subsequently mobilize to an intermediate hematopoietic site known as the caudal hematopoietic tissue (CHT) and finally colonize the kidney for adult hematopoiesis. Despite substantial understanding of the ontogeny of HSPCs, the molecular basis governing migration, colonization and maintenance of HSPCs remains to be explored fully. Here, we report the isolation and characterization of two zebrafish mutants, rumba(hkz1) and samba(hkz2), that are defective in generating definitive hematopoiesis. We find that HSPC initiation in the VDA and subsequent homing to the CHT are not affected in these two mutants. However, the further development of HSPCs in the CHT is compromised in both mutants. Positional cloning reveals that Rumba is a novel nuclear C2H2 zinc-finger factor with unknown function and samba encodes an evolutionarily conserved protein that is homologous to human augmin complex subunit 3 (HAUS3). Furthermore, we show that these two factors independently regulate cell cycle progression of HSPCs and are cell autonomously required for HPSC development in the CHT. Our study identifies Rumba and Haus3 as two essential regulators of HSPC maintenance during zebrafish fetal hematopoiesis.

Links

PubMed Online version:10.1242/dev.054536

Keywords

Animals; Animals, Genetically Modified; Base Sequence; COS Cells; Cercopithecus aethiops; Gene Expression Regulation, Developmental; Hematopoiesis; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/metabolism; Mutation; Zebrafish/embryology; Zebrafish/metabolism; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A2R8Q1K1

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110218-40

P

Seeded From UniProt

complete

DANRE:D2KMS9

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110218-39

P

Seeded From UniProt

complete

DANRE:D2XZ47

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110218-40

P

Seeded From UniProt

complete

DANRE:F1QUN0

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110218-39

P

Seeded From UniProt

complete

DANRE:Q08CD9

involved_in

GO:0060216: definitive hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-110218-40

P

Seeded From UniProt

complete


See also

References

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