title: Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.
abstract: Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch.
authors.affiliation: Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Delloye-Bourgeois
authors.affiliation: Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rama
authors.affiliation: Laboratoire Développement, Evolution et Plasticité du Système Nerveux, Institut de Neurobiologie Alfred Fessard, Gif-sur-Yvette, France.
authors.forename: José
authors.initials: J
authors.lastname: Brito
authors.affiliation: Laboratoire Développement, Evolution et Plasticité du Système Nerveux, Institut de Neurobiologie Alfred Fessard, Gif-sur-Yvette, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Le Douarin
authors.affiliation: Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France. Electronic address: patrick.mehlen@lyon.unicancer.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mehlen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001934:Branchial Region / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival; D002642:Chick Embryo; D004707:Endoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D053823:Hedgehog Proteins
keywords: Apoptosis; CDO; Dependence receptors; Embryonic development; Neural crest cells