title: Kit and foxd3 genetically interact to regulate melanophore survival in zebrafish.
abstract: We have investigated the role of foxd3 activity in conjunction with signaling by the kit tyrosine kinase receptor in zebrafish black pigment cell (melanophore) development. As loss-of-function of these molecules individually has distinct effects on melanophore number, we have examined the phenotype of double mutants. Individuals with a null mutation in kit have fewer melanophores than wild-type, with cells lost through death. When kit mutants are injected with foxd3 antisense morpholino oligonucleotides or crossed with a foxd3 zebrafish mutant, they have more melanophores than their uninjected or foxd3+ counterparts. Examination of foxd3 loss-of-function in two additional kit mutants that differentially alter kit-dependent migration and survival indicates a change in melanophore number in survival mutants only. Consistently, TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) analysis confirms a partial rescue of melanophores from cell death. Ectopic expression of foxd3 indicates that foxd3 promotes early melanophore death only when kit is inactive. Taken together, these data suggest a kit-dependent role for foxd3 in the regulation of melanophore survival.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, USA. cdcooper@vancouver.wsu.edu
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Cooper
authors.forename: Tor H
authors.initials: TH
authors.lastname: Linbo
authors.forename: David W
authors.initials: DW
authors.lastname: Raible
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008543:Melanins / Q000096:biosynthesis; D008547:Melanophores / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D008543:Melanins; D029961:Zebrafish Proteins; C491002:foxd3 protein, zebrafish; D019009:Proto-Oncogene Proteins c-kit