2005 Fiscal Year Final Research Report Summary
Molecular mechanism of the formation and differentiation of hemangioblast
| Project/Area Number |
16370095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWAHARA Atsuo Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 科学技術振興助教授 (10362518)
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| Co-Investigator(Kenkyū-buntansha) |
HANAOKA Ryuki Kyoto University, Graduate School of Medicine, Postdoctoral Fellow, 医学研究科, 科学技術振興研究員 (70362530)
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| Project Period (FY) |
2004 – 2005
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| Keywords | zebrafish / hematopoietic development / functional analysis / hemangioblast |
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| Research Abstract |
We have performed in situ-based screening to identify genes that are specifically expressed in the blood island where both blood and endothelial cells are generated. In this process, we have isolated the heme synthesis enzymes and further examined the function of CPO (coproporphyrinogen oxidase) during zebrafish erythrogenesis. Knockdown analysis of CPO using anti-sense morpholinos (CPO-MO) caused the strong suppression of hemoglobin production, and the maturation of erythorocyte is morphologically arrested. These results suggest that CPO plays important roles in zebrafish erythrogenesis. Next, we examined the regulation of CPO expression. In zebrafish, both GATA1 and biklf transcriptional factors are essential for the blood cell maturation. Interestingly, CPO promoter region has DNA binding sites for both factors. We found that CPO expression is strongly suppressed when biklf-morpholino was injected into vlt mutant embryos (lacking functional GATA1 gene). In contrast, CPO is ectopically induced when both GATA1 and biklf RNAs are injected into two-cell stage embryos. These results suggest that GATA1 and biklf cooperatively contribute the regulation of CPO expression.
We have additionally isolated a novel gene, b819 gene that is restrictedly expressed in the blood island. This gene has no homology to any known protein, but primary structure presents a possible membrane protein. Knockdown analysis of b819 gene induced the suppression of blood cells production and the disorganization of network formation of blood vessels. Since both blood and endothelial cells are produced from the common precursor "hemangioblast", b819 gene may be a critical regulator in this process. Further studies will be required to reveal how b819 gene contributes the development of blood and endothelial cells during early embryogenesis.
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