Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves.

Abstract:

: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.

journal_name

Mol Biol Cell

authors

Hoshino H,Uchida T,Otsuki T,Kawamoto S,Okubo K,Takeichi M,Chisaka O

doi

10.1091/mbc.e06-08-0733

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

1143-52

issue

4

eissn

1059-1524

issn

1939-4586

pii

E06-08-0733

journal_volume

18

pub_type

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