An integrated transcriptional analysis of the developing human retina

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Biomarkers / metabolism
  • Cilia / metabolism
  • Fetus / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental
  • Organogenesis / genetics
  • Photoreceptor Cells, Vertebrate / cytology
  • Photoreceptor Cells, Vertebrate / metabolism
  • Principal Component Analysis
  • RNA / genetics
  • RNA / metabolism
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA, Circular
  • Retina / cytology
  • Retina / embryology*
  • Retina / metabolism*
  • Retina / ultrastructure
  • Transcriptome / genetics


  • Biomarkers
  • RNA Precursors
  • RNA, Circular
  • RNA