Role of the RNA-binding proteins Msi1 and Msi2 in ocular lens development

• Arjun Parab, Biological Sciences, University of Delaware

• Salil Lachke, Biological Sciences, University of Delaware
• Sangeetha Kharidehal, , University of Delaware

The ocular lens is a transparent tissue that focuses light on to the retina for high-resolution vision. The development of the mammalian lens is a complex process which requires precise spatiotemporal gene regulation at transcriptional and post-transcriptional level. Perturbation of this process can lead to ocular birth-defects such as cataracts. Therefore, understanding of lens development is important to uncover the genetic basis of lens defects. Over the years, several genes have been linked to lens defects including transcription factors, and signaling proteins. However, the functional role of RNA-binding proteins (RBPs) that mediate post-transcriptional control in the lens has not been well understood. RBPs control various aspects of the RNA lifecycle in both nucleus and cytoplasm. In the nucleus, they can control events such as transcription, splicing, and polyadenylation. In the cytoplasm, they can enhance or suppress translation, control stability or decay of specific mRNAs and mediate the localization of mRNA thereby regulating downstream signaling pathways. To identify significant RBPs in the lens development process, the Lachke laboratory has developed the bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery). iSyTE is a database that allows the user to predict and prioritize candidate genes potentially involved in lens biology. Thus far, iSyTE has successfully predicted several RBPs, namely Tdrd7, Celf1, and Caprin2, linked to lens development and cataract. Using this tool, we identified two RBPs belonging to the Musashi family, Msi1 and Msi2, that are well known for their role in the maintenance of stem cells and neural precursor cells. Previous studies on double knockout of Msi1 and Msi2 have shown that they play a role in retinal photoreceptor cells. However, the function of Msi1 and Msi2 have not been examined in the lens. We used antibodies against these proteins to show that Msi1 and Msi2 are dynamically expressed in moue lens development, in turn, validating iSyTE’s prediction. Currently, we are using the Cre-loxP system to generate lens-specific conditional knockout mice to further elucidate their functional role. Together, these studies will uncover the function of Msi1 and Msi2 in lens development.