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Functional Analyses of Protocadherin 10 in Embryonic Development of Central Nervous System and Paraxial Mesoderm

原钙粘蛋白10在中枢神经系统和近轴中胚层胚胎发育中的功能分析

基本信息

批准号：
17590147
负责人：
MURAKAMI Tohru
金额：
$ 2.24万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

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 … More 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

研究人员和合作者研究了Protocadherin-10（Pcdh 1 O）和其他钙粘蛋白在斑马鱼发育中的生物学功能。原位杂交（ISH）结果显示，pcdh 1 Ob在近轴中胚层（PAM）、发育中的体节、松果体、间脑和耳囊附近均有表达。在PAM和体节中的表达随着体节成熟而减少。Pcdh 1 Ob的显性负性形式和pcdh 1 Ob的反义Morpholino干扰PAM的收敛和体节分割。比较研究表明，pcdh 10 b和pcdh 8在PAM和近轴的差异表达。我们认为Pcdh 10 b参与PAM的聚合和体节的分割，Pcdh 8和Pcdh 10 b的差异粘附在体节和近轴细胞的形态发生机制中起作用。我们克隆 ...更多信息人类K-钙粘蛋白的斑马鱼同源物。整体原位杂交显示，cdh 6除了在中枢和外周神经系统中表达外，还在原肾管和肾单位原基中表达。注射针对cdh 6的MO（cdh 6 MOs）的胚胎在30 hpf时表现出发育缺陷，包括头部小、体轴弯曲、卵黄延伸短和尾部短弯曲，并且在42 hpf时胸部出现水肿。注射cdh 6 MO的胚胎进行原位杂交与原肾标记，wt 1和pax2.1，检查前肾管和肾单位原基的前区的干扰发展。组织学检查显示原肾畸形，表现为异常融合的肾小球原基、融合或异常弯曲的原肾小管原基和变细的原肾管。这些结果表明cdh 6在斑马鱼胚胎原肾的发育中起着关键作用。在中枢神经系统、咽弓和肠原基均有表达。目前，研究结果将汇编成一份科学报告。少