Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves
Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves
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DOI：
10.1091/mbc.e06-08-0733
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Chisaka, Osamu
中科院分区：
文献类型：
--
作者：
Hoshino, Hideharu;Uchida, Tsukasa;Chisaka, Osamu
在它们向外周迁移的过程中，颅神经嵴细胞（NCC）被毗邻菱形节（r）3和5的间充质中的ErbB 4依赖性线索排斥，菱形节（r）3和5是分段的后脑神经节。ErbB 4具有许多配体，但在上述系统中哪些配体起作用尚未明确确定。在这里，我们发现，cornichon样蛋白/cornichon同源物2（CNIL/CNIH 2）基因表达在发展中的鸡r3和r5。在细胞培养系统中，其产物促进ErbB 4的配体之一肝素结合表皮生长因子样生长因子（HB-EGF）的分泌。当CNIL的功能在鸡胚中受到干扰，通过强制表达的截断形式的CNIL，NCC的分布受到影响，这导致颅感觉神经节之间的异常神经纤维连接。此外，用siRNA敲低CNIL或HB-EGF产生类似的表型。这种表型与ErbB 4基因敲除小鼠胚胎的表型非常相似。由于HB-EGF在胚胎后脑中均匀表达，CNIL似乎将HB-EGF作用的位点限制在与ErbB 4一致的r3和r5。
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 mouse embryos. Because 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.