Affiliation:
1. Institute of Genetics and Cancer, University of Edinburgh 1 MRC Human Genetics Unit , , Edinburgh EH4 2XU, UK
2. School of Informatics, University of Edinburgh 2 , Edinburgh EH8 9AB, UK
Abstract
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
1 articles.
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