Transcriptome analysis of the zebrafish atoh7-/- Mutant, lakritz , highlights Atoh7-dependent genetic networks with potential implications for human eye diseases

FASEB BioAdvances
G. CovelloLucia Poggi

Abstract

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 ...Continue Reading

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Methods Mentioned

BETA
transgenic
genotyping
biopsies
PCR
GTPase

Software Mentioned

Cytoscape
KOBAS
DB
Fiji
ComBat package
Limma
GraphPad
Prism
ctrlMO
WGCNA

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