Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis

Files in This Item:
File Description SizeFormat 
Yin_2014_12864_2014_Article_6503.pdf2.41 MBAdobe PDFDownload
Title: Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis
Authors: Yin, Jun
Morrissey, Maria
Shine, Lisa
Kennedy, Ciarán
Higgins, D. (Des)
Kennedy, Breandán
Permanent link: http://hdl.handle.net/10197/8313
Date: 30-Sep-2014
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.
Funding Details: Irish Research Council for Science, Engineering and Technology
Type of material: Journal Article
Publisher: BioMed Central
Copyright (published version): 2014 the Authors
Keywords: Retinal homeobox transcription factor (Rx);Gene expression;Eye development
DOI: 10.1186/1471-2164-15-825
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

Show full item record

SCOPUSTM   
Citations 50

8
Last Week
0
Last month
checked on Jun 23, 2018

Download(s) 50

26
checked on May 25, 2018

Google ScholarTM

Check

Altmetric


This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.