PT - JOURNAL ARTICLE AU - Jesse Sundar AU - Fatimah Matalkah AU - Bohye Jeong AU - Peter Stoilov AU - Visvanathan Ramamurthy TI - A critical role for MSI1 and MSI2 in photoreceptor morphogenesis AID - 10.1101/2020.01.25.919761 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.25.919761 4099 - http://biorxiv.org/content/early/2020/01/26/2020.01.25.919761.short 4100 - http://biorxiv.org/content/early/2020/01/26/2020.01.25.919761.full AB - We previously proposed a role for the Musashi proteins, MSI1 and MSI2, in photoreceptor cell development that is mediated by their ability to control alternative splicing. Photoreceptors with simultaneous deletion of Msi1 and Msi2 did not respond to light, displayed severely disrupted OS morphology and axonemal defects. At postnatal day 5, we observed an increase in proliferating retinal progenitor cells in the knockout animals, suggesting delay in photoreceptor development. The loss of Musashi prevented the use of photoreceptor-specific exons in transcripts important for OS morphogenesis, ciliogenesis and synaptic transmission. However, deletion of the photoreceptor-specific exons in Ttc8, Cc2d2a, Cep290, Cacna2d4, and Slc17a7 did not impair retinal development or visual function. We demonstrate a critical role for Musashi in the morphogenesis of terminally differentiated photoreceptor neurons. This role is in stark contrast with the canonical function of the two proteins in maintenance and renewal of stem cells.