microRNA Function in Zebrafish Development and Regeneration

Abstract

microRNAs (miRNAs) are a family of highly conserved small noncoding RNAs that post transcriptionally regulate gene expression and play important roles in many cellular processes during development and regeneration. The work presented in this thesis focuses on discovering functions of miRNAs in craniofacial development and retina regeneration in zebrafish. Chapter II describes the role of miR-27 in regulating chondrogenesis during pharyngeal morphogenesis. Chondrogenesis in the pharyngeal arches involves differentiation of cranial neural crest cells into chondrocytes, tightly regulated by temporal intracellular and extracellular cues. miR-27 is highly enriched in the pharyngeal arches and acts as a positive regulator of chondrogenesis by controlling the activity of Focal Adhesion Complex. Chapter III focuses on retina regeneration in adult zebrafish and describes how miR-216 regulates the initiation of Müller glia (MG) dependent retina regeneration. Unlike the adult mammalian retina, MG in the adult zebrafish retina are able to dedifferentiate into a ‘stem cell’-like state and give rise to multipotent progenitor cells upon retinal damage. miR-216a is downregulated in MG after constant intense light lesioning allowing upregulation of the H3K79 methyltransferase Dot1l which is required for MG reprogramming and proliferation downstream of miR-216a. Chapter IV presents a genome-wide transcriptome analysis of MG dedifferentiation during retina regeneration serving as a resource for the identification of potential therapeutic targets.