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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cells, Cultured
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Chick Embryo
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Cloning, Molecular
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Cranial Nerves / embryology*
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Cranial Nerves / metabolism
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Cranial Nerves / pathology
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Egg Proteins / genetics
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Egg Proteins / metabolism
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / metabolism*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Gene Expression Regulation, Developmental
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Heparin-binding EGF-like Growth Factor
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Humans
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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RNA, Small Interfering
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Receptor, ErbB-4
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Rhombencephalon / embryology
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Rhombencephalon / pathology
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Signal Transduction
Substances
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Cnih protein, mouse
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Egg Proteins
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HBEGF protein, human
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Hbegf protein, mouse
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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RNA, Small Interfering
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Epidermal Growth Factor
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ERBB4 protein, human
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ErbB Receptors
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Erbb4 protein, mouse
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Receptor, ErbB-4