Poster abstracts
Poster number 26 submitted by Jade Hostetler
Characterizing the Functions of LncRNAs in Retina Development
Jade Enright Hostetler (John F Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine), Xiaodong Zhang (John F Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine), Shiming Chen (John F Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine), Philip A. Ruzycki (John F Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine), Seth Blackshaw (Department of Neuroscience, Johns Hopkins University School of Medicine), Brian S. Clark (John F Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine)
Abstract:
Long noncoding RNAs (lncRNAs) display pervasive expression and function in the developing nervous system (1,2) The accessibility and simple organization of the vertebrate retina provide a valuable model for understanding the molecular dynamics underlying nervous system development. A single pool of retinal progenitor cells (RPCs) gives rise to the seven major cell types of the retina (six neuronal, one glial) in a conserved overlapping temporal order, requiring precise temporal control of gene regulatory networks, neurogenesis, and cell fate specification(3). Temporal profiling of gene expression in the retina has demonstrated differential expression of lncRNAs throughout development, however determinations of lncRNA function during retinal development remain limited(4). We hypothesize that lncRNAs regulate the coordination and timing of cell fate specification, neurogenesis, and differentiation in the developing retina. In this study, we identify numerous lncRNAs with dynamic temporal expression and characterize the function of the late RPC enriched lncRNA Gm11454, which we have named Peanut. Using an overexpression model in mice, we identify that Peanut promotes rod photoreceptor fate and neurogenesis of retinal progenitor cells (RPCs) via inhibition of Notch signaling and regulating expression of neighboring gene Tox2. A novel Peanut knockout mouse model demonstrates that Peanut is required for proper visual function and photoreceptor gene expression. Finally, we determine that Peanut is necessary for proper cell cycle progression and neurogenesis. Ongoing work seeks to elucidate the direct mechanism of action of Peanut; chromatin enrichment of Peanut suggests that Peanut binds chromatin to regulate gene expression. Overall, our results characterize the function of a novel lncRNA as a regulator of RPC neurogenesis and differentiation and support the importance of lncRNAs in the developing retina.
References:
1. Mercer, Tim R., Marcel E. Dinger, Susan M. Sunkin, Mark F. Mehler, and John S. Mattick. 2008. “Specific Expression of Long Noncoding RNAs in the Mouse Brain.” Proceedings of the National Academy of Sciences 105 (2): 716–21.
2. Sauvageau, Martin, Loyal A Goff, Simona Lodato, Boyan Bonev, Abigail F Groff, et al. 2013. “Multiple Knockout Mouse Models Reveal LincRNAs Are Required for Life and Brain Development.” ELife 2 (December).
3. Bassett, Erin A., and Valerie A. Wallace. 2012. “Cell Fate Determination in the Vertebrate Retina.” Trends in Neurosciences 35 (9): 565–73.
4. Kong, Kangjie, Peiyuan Wang, Zihong Xie, Lu Wang, Jiaxuan Jiang, et al. 2023. “Integrated Transcriptome Analysis of Long Noncoding RNA and MRNA in Developing and Aging Mouse Retina.” Scientific Data 10 (1): 653.
Keywords: LncRNA, Development , Retina