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Development. 2019 Jan 29;146(2). pii: dev169474. doi: 10.1242/dev.169474.

An integrated transcriptional analysis of the developing human retina.

Author information

1
Institute of Genetic Medicine, Newcastle University, Newcastle NE1 3BZ, UK.
2
Lions Eye Institute, 2 Verdun Street, Nedlands, Perth, WA 6009, Australia.
3
School of Computing, Newcastle University, Newcastle NE4 5TG, UK.
4
Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK.
5
European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK.
6
EM Research Services, Newcastle University, Newcastle NE2 4HH, UK.
7
Institute of Genetic Medicine, Newcastle University, Newcastle NE1 3BZ, UK majlinda.lako@ncl.ac.uk.

Abstract

The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.

KEYWORDS:

Alternative splicing; Circular RNAs; Developing human retina; Immunohistochemistry; Retinal cells; Transcriptome

PMID:
30696714
PMCID:
PMC6361134
DOI:
10.1242/dev.169474
[Indexed for MEDLINE]
Free PMC Article

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