title: Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates.
abstract: Waardenburg-Shah syndrome combines the reduced enteric nervous system characteristic of Hirschsprung's disease with reduced pigment cell number, although the cell biological basis of the disease is unclear. We have analysed a zebrafish Waardenburg-Shah syndrome model. We show that the colourless gene encodes a sox10 homologue, identify sox10 lesions in mutant alleles and rescue the mutant phenotype by ectopic sox10 expression. Using iontophoretic labelling of neural crest cells, we demonstrate that colourless mutant neural crest cells form ectomesenchymal fates. By contrast, neural crest cells which in wild types form non-ectomesenchymal fates generally fail to migrate and do not overtly differentiate. These cells die by apoptosis between 35 and 45 hours post fertilisation. We provide evidence that melanophore defects in colourless mutants can be largely explained by disruption of nacre/mitf expression. We propose that all defects of affected crest derivatives are consistent with a primary role for colourless/sox10 in specification of non-ectomesenchymal crest derivatives. This suggests a novel mechanism for the aetiology of Waardenburg-Shah syndrome in which affected neural crest derivatives fail to be generated from the neural crest.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Dutton
authors.forename: A
authors.initials: A
authors.lastname: Pauliny
authors.forename: S S
authors.initials: SS
authors.lastname: Lopes
authors.forename: S
authors.initials: S
authors.lastname: Elworthy
authors.forename: T J
authors.initials: TJ
authors.lastname: Carney
authors.forename: J
authors.initials: J
authors.lastname: Rauch
authors.forename: R
authors.initials: R
authors.lastname: Geisler
authors.forename: P
authors.initials: P
authors.lastname: Haffter
authors.forename: R N
authors.initials: RN
authors.lastname: Kelsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006627:Hirschsprung Disease / Q000235:genetics*; D008547:Melanophores / Q000378:metabolism; D008648:Mesoderm; D008969:Molecular Sequence Data; D009154:Mutation; D009432:Neural Crest / Q000166:cytology*; D010859:Pigmentation Disorders / Q000235:genetics*; D055757:SOXE Transcription Factors; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C442229:sox10 protein, zebrafish