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Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators
The AML/RUNX family of transcription factors plays important roles in hematopoiesis, neurogenesis, bone development, and segmentation in vertebrate embryos. The aim of this study was to isolate runt-related genes in a genetically and embryologically exploitable system, the zebrafish, and characteriz...
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Published in: | Experimental hematology 2002-12, Vol.30 (12), p.1381-1389 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The AML/RUNX family of transcription factors plays important roles in hematopoiesis, neurogenesis, bone development, and segmentation in vertebrate embryos. The aim of this study was to isolate
runt-related genes in a genetically and embryologically exploitable system, the zebrafish, and characterize their function during hematopoietic development.
Two
runt-related genes were isolated by degenerate PCR and standard library screening, and a radiation hybrid panel, T51 RH, was used to resolve their chromosomal localization. In situ hybridization demonstrated their expression whereas their transcriptional activity was assessed using an AML1-responsive reporter gene in the MLA 144 T-cell line.
We isolated the zebrafish
runxa and
runxb cDNAs, which encode proteins highly homologous to the human and murine Runx1 (AML1) and Runx3 (AML2) proteins. In contrast to a recent report, we detected
runxa expression in both hematopoietic and neural tissues of the developing zebrafish.
runxa transcripts first appear during segmentation in bilateral mesodermal cells that coexpress one of the earliest blood and endothelial cell markers,
scl/tal-1. By 24 hours postfertilization (hpf),
runxa transcripts are seen in the ventral wall of the dorsal aorta. Hematopoietic
runxa expression is lost in
cloche mutants, which are defective in blood and endothelial cell formation.
runxb transcripts are seen in nonhematopoietic domains. Both Runxa and Runxb transactivate an AML1-responsive human promoter in hematopoietic cells. Genomic localization studies demonstrate that
runxa is located on linkage group 1 (LG1), and the
runxb gene is located on LG13.
Our gene expression analysis strongly suggests that both the functional and spatial aorta-gonad-mesonephros (AGM) region has been conserved throughout evolution. Our
runxa spatiotemporal expression data shed light on the role of vertebrate Runx1/AML1 in primitive vs definitive hematopoietic development. |
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ISSN: | 0301-472X 1873-2399 |
DOI: | 10.1016/S0301-472X(02)00955-4 |