Functional analysis of cnil ; an intra-cellular transporter of EGF-repeat-containing growth factors
CNIL的功能分析;
基本信息
- 批准号:18570195
- 负责人:
- 金额:$ 2.51万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2006
- 资助国家:日本
- 起止时间:2006 至 2007
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
During their migration to the periphery, cranial neural crest cells (NCCs) are repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r) 3 and 5, which are segmented hindbrain neuromeres. ErbB4 has many ligands, but which ligand functions in the above system has not yet been clearly determined. Here we found that a cornichon-like protein/cornichon homolog 2 (CNIL/CNIH2) gene was expressed in the developing chick r3 and r5. In a cell culture system, its product facilitated the secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), one of the ligands of ErbB4. When CNIL function was perturbed in chick embryos by forced expression of a truncated form of CNIL, the distribution of NCCs was affected, which resulted in abnormal nerve fiber connections among the cranial, sensory ganglia. Also, knockdown of CNIL or HB-EGF with siRNAs yielded a similar phenotype. This phenotype closely resembled that of ErbB4 knockout (KO) mouse embryos. Since HB-EGF was uniformly expressed in the embryonic hindbrain, CNIL seems to confine the site of HB-EGF action to r3 and r5 in concert with ErbB4.
在向外周迁移的过程中,颅神经嵴细胞(NCCs)被相邻的间质斜形神经粒(r) 3和5中的erbb4依赖信号所排斥,这些斜形神经粒是分节的后脑神经粒。ErbB4有许多配体,但在上述体系中究竟是哪一种配体起作用还没有明确的确定。本研究发现,在发育中的小鸡r3和r5中表达了一个cornicon样蛋白/ cornicon同源基因2 (CNIL/CNIH2)。在细胞培养系统中,其产物促进ErbB4配体之一的肝素结合表皮生长因子样生长因子(HB-EGF)的分泌。当鸡胚中CNIL的功能被强迫表达截断后的CNIL干扰时,NCCs的分布受到影响,导致颅神经节、感觉神经节之间的神经纤维连接异常。同样,用sirna敲除CNIL或HB-EGF也会产生类似的表型。这种表型与ErbB4敲除(KO)小鼠胚胎非常相似。由于HB-EGF在胚胎后脑中均匀表达,CNIL似乎将HB-EGF的作用位点限制在r3和r5,并与ErbB4一致。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves
- DOI:10.1091/mbc.e06-08-0733
- 发表时间:2007-04-01
- 期刊:
- 影响因子:3.3
- 作者:Hoshino, Hideharu;Uchida, Tsukasa;Chisaka, Osamu
- 通讯作者:Chisaka, Osamu
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CHISAKA Osamu其他文献
CHISAKA Osamu的其他文献
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{{ truncateString('CHISAKA Osamu', 18)}}的其他基金
Analysis of the Hoxa3 gene that regulates the migration/differentiation of the cranial neural crest cells.
分析调节颅神经嵴细胞迁移/分化的 Hoxa3 基因。
- 批准号:
15570177 - 财政年份:2003
- 资助金额:
$ 2.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)