title: Neural crest cell deficiency of c-myc causes skull and hearing defects.
abstract: The proto-oncogene c-myc has a central role in multiple processes important for embryonic development, including cell proliferation, growth, apoptosis, and differentiation. We have investigated the role of c-myc in neural crest by using Wnt1-Cre-mediated deletion of a conditional mutation of the c-myc gene. c-myc deficiency in neural crest resulted in viable adult mice that have defects in coat color, skull frontal bone, and middle ear ossicle development. Physiological hearing studies demonstrated a significant hearing deficit in the mutant mice. In this report, we focus on the craniofacial and hearing defects. To further examine neural crest cells affected by c-myc deficiency, we fate mapped Wnt1-Cre expressing neural crest cells using the ROSA26 Cre reporter transgene. The phenotype obtained demonstrates the critical role that c-myc has in neural crest during craniofacial development as well as in providing a model for examining human congenital skull defects and deafness.
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Wei
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Chen
authors.forename: Kevan
authors.initials: K
authors.lastname: Akrami
authors.forename: Gary C
authors.initials: GC
authors.lastname: Galbraith
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Lopez
authors.forename: Fabian
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D017930:Genes, Reporter; D034381:Hearing Loss / Q000235:genetics*; D019426:Integrases / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D022661:RNA, Untranslated; D017384:Sequence Deletion; D012886:Skull / Q000002:abnormalities*; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D022661:RNA, Untranslated; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C045073:Cre recombinase; D019426:Integrases