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    Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis

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    Authors
    Yin, Jun
    Morrissey, Maria E
    Shine, Lisa
    Kennedy, Ciarán
    Higgins, Desmond G
    Kennedy, Breandán N
    Issue Date
    2014-09-30
    Keywords
    EYE DISORDER
    GENETICS
    
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    Citation
    Yin J et al. Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis. BMC Genomics. 2014 Sep 30;15(1):825
    URI
    http://dx.doi.org/10.1186/1471-2164-15-825
    http://hdl.handle.net/10147/332083
    Abstract
    Abstract Background The genetic cascades underpinning vertebrate early eye morphogenesis are poorly understood. One gene family essential for eye morphogenesis encodes the retinal homeobox (Rx) transcription factors. Mutations in the human retinal homeobox gene (RAX) can lead to gross morphological phenotypes ranging from microphthalmia to anophthalmia. Zebrafish rx3 null mutants produce a similar striking eyeless phenotype with an associated expanded forebrain. Thus, we used zebrafish rx3 -/- mutants as a model to uncover an Rx3-regulated gene network during early eye morphogenesis. Results Rx3-regulated genes were identified using whole transcriptomic sequencing (RNA-seq) of rx3 -/- mutants and morphologically wild-type siblings during optic vesicle morphogenesis. A gene co-expression network was then constructed for the Rx3-regulated genes, identifying gene cross-talk during early eye development. Genes highly connected in the network are hub genes, which tend to exhibit higher expression changes between rx3 -/- mutants and normal phenotype siblings. Hub genes down-regulated in rx3 -/- mutants encompass homeodomain transcription factors and mediators of retinoid-signaling, both associated with eye development and known human eye disorders. In contrast, genes up-regulated in rx3 -/- mutants are centered on Wnt signaling pathways, associated with brain development and disorders. The temporal expression pattern of Rx3-regulated genes was further profiled during early development from maternal stage until visual function is fully mature. Rx3-regulated genes exhibited synchronized expression patterns, and a transition of gene expression during the early segmentation stage when Rx3 was highly expressed. Furthermore, most of these deregulated genes are enriched with multiple RAX-binding motif sequences on the gene promoter. Conclusions Here, we assembled a comprehensive model of Rx3-regulated genes during early eye morphogenesis. Rx3 promotes optic vesicle morphogenesis and represses brain development through a highly correlated and modulated network, exhibiting repression of genes mediating Wnt signaling and concomitant enhanced expression of homeodomain transcription factors and retinoid-signaling genes.
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    Language
    en
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