title: A new mib allele with a chromosomal deletion covering foxc1a exhibits anterior somite specification defect.
abstract: mib(nn2002), found from an allele screen, showed early segmentation defect and severe cell death phenotypes, which are different from previously known mib mutants. Despite distinct morphological phenotypes, the typical mib molecular phenotypes: her4 down-regulation, neurogenic phenotype and cold sensitive dlc expression pattern, still remained. The linkage analysis also indicated that mib(nn2002) is a new mib allele. Failure of specification in anterior 7-10 somites is likely due to lack of foxc1a expression in mib(nn2002) homozygotes. Somites and somite markers gradually appeared after 7-10 somite stage, suggesting that foxc1a is only essential for the formation of anterior 7-10 somites. Apoptosis began around 16-somite stage with p53 up-regulation. To find the possible links of mib, foxc1a and apoptosis, transcriptome analysis was employed. About 140 genes, including wnt3a, foxc1a and mib, were not detected in the homozygotes. Overexpression of foxc1a mRNA in mib(nn2002) homozygotes partially rescued the anterior somite specification. In the process of characterizing mib(nn2002) mutation, we integrated the scaffolds containing mib locus into chromosome 2 (or linkage group 2, LG2) based on synteny comparison and transcriptome results. Genomic PCR analysis further supported the conclusion and showed that mib(nn2002) has a chromosomal deletion with the size of about 9.6 Mbp.
authors.affiliation: 1] Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan [2] Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Taiwan.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Lin
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong.
authors.forename: Keng
authors.initials: K
authors.lastname: Po Lai
authors.affiliation: School of Life Sciences, Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jing-Woei
authors.initials: JW
authors.lastname: Li
authors.affiliation: School of Life Sciences, Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ting-Fung
authors.initials: TF
authors.lastname: Chan
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.
authors.forename: May-Su
authors.initials: MS
authors.lastname: You
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong.
authors.forename: William Ka Fai
authors.initials: WK
authors.lastname: Tse
authors.affiliation: 1] Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan [2] Biotechnology Center, National Chung Hsing University, Taiwan [3] Institute of Molecular and Cellular Biology, National Taiwan University, Taiwan.
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Jiang
mesh_terms: D000483:Alleles; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D002872:Chromosome Deletion; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D006720:Homozygote; D009154:Mutation; D038081:Organogenesis / Q000235:genetics; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D019170:Somites / Q000378:metabolism* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; C426857:Foxc1a protein, zebrafish; D029961:Zebrafish Proteins; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish