Visual perception begins in the eye, where light is captured and converted into an electrochemical signals by a specialized sensory organ, the retina. These signals are then send through the optic nerve to higher centers in the brain for further processing necessary for perception. Vision requires correct development of different type of retinal neurons and their assembly into a complex regulatory network allowing proper functionality. During retinogenesis differentiation of distinct cell populations is carried out in a multi-step processes that involves cell cycle exit, migration, and changes of cell morphology. Sequential control of gene expression is necessary for the final maturation and function of specific retinal cells. Defects in the gene expression frequently results in retinal diseases or increase the susceptibility to disease.
Regulatory RNAs, like small microRNAs (miRNAs) or long non-coding RNAs (lincRNAs), are important factors controlling gene expression. Hundreds of different miRNAs have been identified in mammals. This class of RNAs is thought to repress protein synthesis by inhibiting translation of messenger RNAs and causing their destabilization. miRNAs are implicated in control of all fundamental cellular processes, including proliferation, differentiation and cell fate determination or apoptosis, and most of them are expressed in a development- or tissue-specific manner. Their role in controlling development and physiology of retinal neurons remains poorly understood.
Photoreceptor cells - rods and cones, mediate the first step in vision, capturing light and carrying out phototransduction. Our previous studies revealed that several miRNAs are predominantly expressed in mature photoreceptors and their levels are differently regulated in light and dark conditions.
The project goal is to analyze regulation of the miRNAs expression during photoreceptors development and search for potential gene targets, which controlled by miRNAs allow proper rods and cones differentiation and maturation. Investigating the mechanisms of the photoreceptors development controlled by miRNAs is of specific importance to gain a basic knowledge of how post-transcriptional regulation of the gene expression influences vision establishment and function. Finding a unique miRNAs signature for regulation of rods and cones development may help to establish new future approaches for gene therapy or for restoration of visual functions in eye diseases.
This interdisciplinary project, bringing together integrated epigenetic and neurobiology areas, will be conducted in the Friedrich Miescher Institute (FMI) in Basel, the one of the leading biomedical research centers in the Europe.