2006 Fiscal Year Final Research Report Summary
Functional Analyses of Protocadherin 10 in Embryonic Development of Central Nervous System and Paraxial Mesoderm
| Project/Area Number |
17590147
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Gunma University |
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Principal Investigator |
MURAKAMI Tohru Gunma University, Graduate School of Medicine, Assistant Professor, 大学院医学系研究科, 講師 (10239494)
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| Project Period (FY) |
2005 – 2006
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| Keywords | cadherin / protocadherin / central nervous system / somite / pharyngeal arch / pronephros / zebrafish / Morpholino |
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| Research Abstract |
The investigator and collaborators studied biological functions of Protocadherin-lO (Pcdh1O) and other cadherins in zebrafish development. In situ hybridization (ISH) showed that pcdh1Ob was expressed in the paraxial mesoderm (PAM) and developing somites, and in the pineal body, the diencephalon and the vicinity of otocysts. Expression in PAM and somites decreased during somite maturation. A dominant-negative form of Pcdh1Ob and anti-sense Morpholino of pcdh1Ob disturbed convergence of PAM and somite segmentation. Comparative studies showed that differential expressions of pcdh1Ob and pcdh8 in PAM and the adaxial. We propose that Pcdh1Ob is involved in the convergence of PAM and somite segmentation, and that differential adhesion of Pcdh8 and Pcdh10b plays a role in the morphogenic machinery of somites and adaxial cells.
We performed functional analyses of cadherin-6 (cdh6) in zebrafish nephrogenesis using antisense morpholino oligonucleotide (MO) inhibition combined with ISH. We cloned
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a zebrafish homolog of human K-cadherin. Whole-mount ISH showed that cdh6 is expressed in the pronephric ducts and nephron primordium in addition to the central and peripheral nervous systems. Embryos injected with MOs directed against cdh6 (cdh6MOs) showed developmental defects including small head, body axis curvature, short yolk extension, and short bent tail by 30 hpf, and edema appeared in the thorax by 42 hpf. Embryos injected with cdh6MOs were subjected to in situ hybridization with pronephric markers, wtl and pax2.1, to examine disturbed development of the anterior region of the pronephric ducts and the nephron primordia. Histological studies showed malformation of the pronephros as abnormally fused glomerulus primordia, fused or abnormally bent pronephric tubule anlage, and thin pronephric ducts. These results suggested that cdh6 plays pivotal roles in development of the pronephros in zebrafish embryos.
We also studied zebrafish Protocadherin-18. It was expressed central nervous system, pharyngeal arches and gut primodia. The results are currently to be compiled as a scientific report. Less
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