Kit and foxd3 genetically interact to regulate melanophore survival in zebrafish.
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.
Cooper
Cynthia D
CD
Department of Biological Structure, University of Washington, Seattle, Washington, USA. cdcooper@vancouver.wsu.edu
Linbo
Tor H
TH
Raible
David W
DW
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*
D051858:Forkhead Transcription Factors; D008543:Melanins; D029961:Zebrafish Proteins; C491002:foxd3 protein, zebrafish; D019009:Proto-Oncogene Proteins c-kit