RRC ID 78565
Author Owen LJ, Rainger J, Bengani H, Kilanowski F, FitzPatrick DR, Papanastasiou AS.
Title Characterization of an eye field-like state during optic vesicle organoid development.
Journal Development
Abstract Specification of the eye field (EF) within the neural plate marks the earliest detectable stage of eye development. Experimental evidence, primarily from non-mammalian model systems, indicates that the stable formation of this group of cells requires the activation of a set of key transcription factors. This crucial event is challenging to probe in mammals and, quantitatively, little is known regarding the regulation of the transition of cells to this ocular fate. Using optic vesicle organoids to model the onset of the EF, we generate time-course transcriptomic data allowing us to identify dynamic gene expression programmes that characterize this cellular-state transition. Integrating this with chromatin accessibility data suggests a direct role of canonical EF transcription factors in regulating these gene expression changes, and highlights candidate cis-regulatory elements through which these transcription factors act. Finally, we begin to test a subset of these candidate enhancer elements, within the organoid system, by perturbing the underlying DNA sequence and measuring transcriptomic changes during EF activation.
Volume 150(15)
Published 2023-8-1
DOI 10.1242/dev.201432
PII 316689
PMID 37306293
PMC PMC10445745
MeSH Animals Base Sequence Eye* / metabolism Gene Expression Regulation, Developmental Mammals / genetics Organoids / metabolism Regulatory Sequences, Nucleic Acid Transcription Factors* / metabolism
Human and Animal Cells Rx-GFP K/I EB5(AES0145)