Abstract
Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs) play a significant role. Members of this family are present in the cell as transcripts, but are not translated into proteins. MicroRNAs (miRNAs) are small ncRNAs that act as post-transcriptional regulators. During the last decade, they have been implicated in a variety of biological processes, including the development of the nervous system. On the other hand, long-ncRNAs (lncRNAs) represent a different class of ncRNAs that act mainly through processes involving chromatin remodeling and epigenetic mechanisms. The visual system is a prominent model to investigate the molecular mechanisms underlying neurogenesis or circuit formation and function, including the differentiation of retinal progenitor cells to generate the seven principal cell classes in the retina, pathfinding decisions of retinal ganglion cell axons in order to establish the correct connectivity from the eye to the brain proper, and activity-dependent mechanisms for the functionality of visual circuits. Recent findings have associated ncRNAs in several of these processes and uncovered a new level of complexity for the existing regulatory mechanisms. This review summarizes and highlights the impact of ncRNAs during the development of the vertebrate visual system, with a specific focus on the role of miRNAs and a synopsis regarding recent findings on lncRNAs in the retina.
Highlights
During the development of the nervous system, a sophisticated interplay between different molecules in an organism takes place to generate the correct cell types at the correct time, allow them to migrate to the appropriate places and connect to each other in a proper way to ensure normal functionality
The correct establishment of axial polarity of the retina ensures that retinal ganglion cells (RGCs), the only projection neurons of the eye, form synaptic connections with different brain targets in an appropriate retinotopic manner [4]
In the first part we focus on the family of miRNAs, summarizing the studies that have been carried out to profile their expression pattern in the vertebrate retina and the experiments aimed at their functional characterization during normal retinal development
Summary
During the development of the nervous system, a sophisticated interplay between different molecules in an organism takes place to generate the correct cell types at the correct time, allow them to migrate to the appropriate places and connect to each other in a proper way to ensure normal functionality. In the canonical pathway (Figure 1, middle): MiRNA genes are transcribed by RNA polymerase II to give rise to long primary transcripts (pri-miRNAs), which form hairpin structures. This step is subject to regulation by transcriptional activators or inhibitors (not shown). Other RNAs (Figure 1, right): Exceptions to the canonical pathway have been found for transcripts generated by RNA polymerase III They are first processed in the nucleus in a Drosha-independent manner and transported to the cytosol where they may be subject to a Dicer/Ago-dependent pathway. We discuss the emerging roles of lncRNAs in the retina
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