Abstract

A large portion of the genome is transcribed, but much of the transcriptome lacks protein-coding potential. Transcripts lacking protein-coding potential function instead as noncoding RNAs. Long noncoding RNAs (lncRNAs) are noncoding transcripts over 200 nucleotides which function as molecular scaffolds to regulate gene expression through a wide variety of mechanisms including regulation of chromatin structure and gene transcription. LncRNAs are enriched in the central nervous system and display temporally dynamic expression patterns during development, putatively placing them as regulators of dynamic neurodevelopmental processes. Here we use the retina as a model of neurodevelopment to investigate the functions and mechanisms of lncRNAs in regulating neurogenesis and cell fate specification. Using RNA sequencing data, we identify lncRNAs with temporally dynamic expression patterns as candidate regulators of retinal development and further characterize their retinal cellular expression patterns. We elucidate the function of a novel lncRNA, Peanut (Gm11454), through overexpression and knockout experiments, demonstrating that Peanut regulates progression of the cell cycle to promote neurogenesis and the establishment of photoreceptor gene regulatory networks for proper photoreceptor differentiation and function. Additionally, we show that lncRNAs bind retinal transcription factors, likely providing temporally dynamic modulation of transcription factor activity. Overall, this study further establishes lncRNAs as regulators of retinal development and provides evidence characterizing the mechanistic functions of lncRNAs.

Committee Chair

Brian Clark

Committee Members

Christopher Maher; Kristen Kroll; Shiming Chen; Takeshi Yoshimatsu

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Cell Biology)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

4-24-2026

Language

English (en)

Author's ORCID

https://orcid.org/0000-0002-5051-2288

Available for download on Thursday, April 22, 2027

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