title: White spotting phenotype induced by targeted REST disruption during neural crest specification to a melanocyte cell lineage.
abstract: Neural crest cells (NCCs) emerge from the dorsal region of the neural tube of vertebrate embryos and have the pluripotency to differentiate into both neuronal and non-neuronal lineages including melanocytes. Rest, also known as NRSF (neuro-restrictive silencer factor), is a regulator of neuronal development and function and suggested to be involved in the lineage specification of NCCs. However, further investigations of Rest gene functions in vivo have been hampered by the fact that Rest null mice show early embryonic lethality. To investigate the function of Rest in NCC development, we recently established NCC-specific Rest conditional knockout (CKO) mice and observed their neonatal death. Here, we have established viable heterozygous NCC-specific Rest CKO mice to analyze the function of Rest in an NCC-derived melanocyte cell lineage and found that the white spotting phenotype was associated with the reduction in the number of melanoblasts in the embryonic skin. The Rest deletion induced after the specification to melanocytes did not reduce the number of melanoblasts; therefore, the expression of REST during the early neural crest specification stage was necessary for the normal development of melanoblasts to cover all of the skin.
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D015870:Gene Expression; D018390:Gene Targeting; D017930:Genes, Reporter; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics; D000099229:RE1-Silencing Transcription Factor
chemical_list: D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor