title: Eif3ba regulates cranial neural crest development by modulating p53 in zebrafish.
abstract: Congenital diseases caused by abnormal development of the cranial neural crest usually present craniofacial malformations and heart defects while the precise mechanism is not fully understood. Here, we show that the zebrafish eif3ba mutant caused by pseudo-typed retrovirus insertion exhibited a similar phenotype due to the hypogenesis of cranial neural crest cells (NCCs). The derivatives of cranial NCCs, including the NCC-derived cell population of pharyngeal arches, craniofacial cartilage, pigment cells and the myocardium derived from cardiac NCCs, were affected in this mutant. The expression of several neural crest marker genes, including crestin, dlx2a and nrp2b, was specifically reduced in the cranial regions of the eif3ba mutant. Through fluorescence-tracing of the cranial NCC migration marker nrp2b, we observed reduced intensity of NCC-derived cells in the heart. In addition, p53 was markedly up-regulated in the eif3ba mutant embryos, which correlated with pronounced apoptosis in the cranial area as shown by TUNEL staining. These findings suggest a novel function of eif3ba during embryonic development and a novel level of regulation in the process of cranial NCC development, in addition to providing a potential animal model to mimic congenital diseases due to cranial NCC defects. Furthermore, we report the identification of a novel transgenic fish line Et(gata2a:EGFP)pku418 to trace the migration of cranial NCCs (including cardiac NCCs); this may serve as an invaluable tool for investigating the development and dynamics of cranial NCCs during zebrafish embryogenesis.
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Xia
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Tong
authors.forename: Fang
authors.initials: F
authors.lastname: Liang
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chikin
authors.initials: C
authors.lastname: Kuok
authors.forename: Yingla
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinxing
authors.initials: X
authors.lastname: Liu
authors.forename: Zuoyan
authors.initials: Z
authors.lastname: Zhu
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D002465:Cell Movement; D039621:Eukaryotic Initiation Factor-3 / Q000502:physiology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology*; D012190:Retroviridae / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D039621:Eukaryotic Initiation Factor-3; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C571228:tp53 protein, zebrafish; D049452:Green Fluorescent Proteins
keywords: Cardiac neural crest; Cranial neural crest; Zebrafish; eif3ba; nrp2b; p53