rbm47, a novel RNA binding protein, regulates zebrafish head development

Authors

  • Rui Guan,

    1. Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada
    2. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
    3. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
    4. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital and Cancer Research Institute, Central South, Hunan Province, China
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  • Suzan El-Rass,

    1. Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada
    2. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
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  • David Spillane,

    1. Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada
    2. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
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  • Simon Lam,

    1. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
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  • Yuodong Wang,

    1. Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada
    2. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
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  • Jing Wu,

    1. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
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  • Zhuchu Chen,

    1. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital and Cancer Research Institute, Central South, Hunan Province, China
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  • Anan Wang,

    1. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
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  • Zhengping Jia,

    1. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
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  • Armand Keating,

    1. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
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  • Jim Hu,

    1. Department of Laboratory Medicine and Pathology, University of Toronto & Program in Physiology and Experimental Medicine, Toronto, Canada
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  • Xiao-Yan Wen

    Corresponding author
    1. Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada
    2. Department of Medicine, Physiology and Institute of Medical Science, University of Toronto, Canada
    • Correspondence to: Xiao-Yan Wen, 209 Victoria Street, Room 519, Toronto, Ontario, Canada M5B 1T8. E-mail: x.wen@utoronto.ca

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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. Developmental Dynamics 242:1395–1404, 2013. © 2013 Wiley Periodicals, Inc.

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