title: rbm47, a novel RNA binding protein, regulates zebrafish head development.
abstract: BACKGROUND
  Vertebrate trunk induction requires inhibition of bone morphogenetic protein (BMP) signaling, whereas vertebrate head induction requires concerted inhibition of both Wnt and BMP signaling. RNA binding proteins play diverse roles in embryonic development and their roles in vertebrate head development remain to be elucidated.
  
  
  RESULTS
  We first characterized the human RBM47 as an RNA binding protein that specifically binds RNA but not single-stranded DNA. Next, we knocked down rbm47 gene function in zebrafish using morpholinos targeting the start codon and exon-1/intron-1 splice junction. Down-regulation of rbm47 resulted in headless and small head phenotypes, which can be rescued by a wnt8a blocking morpholino. To further reveal the mechanism of rbm47's role in head development, microarrays were performed to screen genes differentially expressed in normal and knockdown embryos. epcam and a2ml were identified as the most significantly up- and down-regulated genes, respectively. The microarrays also confirmed up-regulation of several genes involved in head development, including gsk3a, otx2, and chordin, which are important regulators of Wnt signaling.
  
  
  CONCLUSIONS
  Altogether, our findings reveal that Rbm47 is a novel RNA-binding protein critical for head formation and embryonic patterning during zebrafish embryogenesis which may act through a Wnt8a signaling pathway.
authors.affiliation: Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada; Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Canada; Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital and Cancer Research Institute, Central South, Hunan Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guan
authors.forename: Suzan
authors.initials: S
authors.lastname: El-Rass
authors.forename: David
authors.initials: D
authors.lastname: Spillane
authors.forename: Simon
authors.initials: S
authors.lastname: Lam
authors.forename: Yuodong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Zhuchu
authors.initials: Z
authors.lastname: Chen
authors.forename: Anan
authors.initials: A
authors.lastname: Wang
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Armand
authors.initials: A
authors.lastname: Keating
authors.forename: Jim
authors.initials: J
authors.lastname: Hu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006257:Head / Q000196:embryology*; D006801:Humans; D017403:In Situ Hybridization; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D060172:Morpholinos; C000589380:RBM47 protein, human; D016601:RNA-Binding Proteins; C000589379:Rbm47 protein, zebrafish; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094521:wnt8a protein, zebrafish
keywords: RNA binding protein; gene knockdown; gene regulation; head development; microarray; morpholino; rbm47; zebrafish