期刊
FASEB BIOADVANCES
卷 2, 期 7, 页码 434-448出版社
WILEY
DOI: 10.1096/fba.2020-00030
关键词
Ath5; human retina; inherited eye diseases; retinal ganglion cells; transcriptome analysis
资金
- Wellcome Trust
- Deutsche Forschungsgemeinschaft Research Grant [PO 1440/1-1]
- Landesgraduiertenforderung (Funding program of the State of Baden Wurttemberg, Germany)
- Australian Research Council [DP140101067, DP190102771]
- State Government of Victoria
- Australian Government
- CONICYT [REDES 150094]
- [ANID/FONDAP/15090007]
Expression of the bHLH transcription protein Atoh7 is a crucial factor conferring competence to retinal progenitor cells for the development of retinal ganglion cells. Several studies have emerged establishing ATOH7 as a retinal disease gene. Remarkably, such studies uncovered ATOH7 variants associated with global eye defects including optic nerve hypoplasia, microphthalmia, retinal vascular disorders, and glaucoma. The complex genetic networks and cellular decisions arising downstream of atoh7 expression, and how their dysregulation cause development of such disease traits remains unknown. To begin to understand such Atoh7-dependent events in vivo, we performed transcriptome analysis of wild-type and atoh7 mutant (lakritz) zebrafish embryos at the onset of retinal ganglion cell differentiation. We investigated in silico interplays of atoh7 and other disease-related genes and pathways. By network reconstruction analysis of differentially expressed genes, we identified gene clusters enriched in retinal development, cell cycle, chromatin remodeling, stress response, and Wnt pathways. By weighted gene coexpression network, we identified coexpression modules affected by the mutation and enriched in retina development genes tightly connected to atoh7. We established the groundwork whereby Atoh7linked cellular and molecular processes can be investigated in the dynamic multitissue environment of the developing normal and diseased vertebrate eye.
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