title: The role of the SPT6 chromatin remodeling factor in zebrafish embryogenesis.
abstract: Somitogenesis is a highly controlled process that results in segmentation of the paraxial mesoderm. Notch pathway activity in the presomitic mesoderm is fundamental for management of synchronized gene expression which is necessary for regulation of somitogenesis. We have isolated an embryonic lethal mutation, SBU2, that causes somite formation defects very similar to Notch pathway mutants. SBU2 mutants generate only 6-7 asymmetrically arranged somites. However, in contrast to Notch pathway mutants, these mutants do not maintain previously formed somite boundaries and by 24 hpf, almost no somite boundaries remain. Other developmental processes disrupted in SBU2 mutants include tail morphogenesis, muscle fiber elongation, pigmentation, circulatory system development and neural differentiation. We demonstrated that these defects are the result of a nonsense mutation within the spt6 gene. spt6 encodes a transcription elongation factor that genetically interacts with the Paf-1 chromatin remodeling complex. SBU2 mutant phenotypes could be rescued by microinjection of spt6 mRNA and microinjection of spt6 morpholinos phenocopied the mutation. Our real-time PCR analysis revealed that Spt6 is essential for the transcriptional response to activation of the Notch pathway. Analysis of sbu2;mib double mutants indicates that Spt6 deficiency suppresses the neurogenic effects of the mib. Altogether, these results demonstrate that Spt6 is critical for somite formation in zebrafish and suggest that some defects observed in spt6 mutants result from alterations in Notch signaling. However, additional Spt6 mutant phenotypes are likely caused by vital functions of Spt6 in other pathways.
authors.affiliation: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Fatma O
authors.initials: FO
authors.lastname: Kok
authors.forename: Emma
authors.initials: E
authors.lastname: Oster
authors.forename: Laura
authors.initials: L
authors.lastname: Mentzer
authors.forename: Jen-Chih
authors.initials: JC
authors.lastname: Hsieh
authors.forename: Clarissa A
authors.initials: CA
authors.lastname: Henry
authors.forename: Howard I
authors.initials: HI
authors.lastname: Sirotkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051880:Receptors, Notch; D014157:Transcription Factors; D029961:Zebrafish Proteins; D004247:DNA