Dicer is essential for proper maturation, composition, and function in the postnatal retina.
Seoyoung Kang, Daniel Larbi, Eik Bruns, Konstantin Hahne, Alireza Khodadadi‐JamayraniD, Chaitra SreenivasaiahiD, Mariana Lima Carneiro, Monica Andrade, Khulan Batsuuri, Shaoheng CheniD, Julia Jager, Suresh ViswanáthaniD, Brian S. ClarkiD, Stefanie G. WohliD
Abstract
microRNAs (miRNAs) play a pivotal role during the early phases of retinal development, but their impact on late-phase retinogenesis is unknown. We depleted miRNAs in late retinal progenitor/precursor cells (RPCs/PCs) via a conditional Dicer knock-out. Optical coherence tomography (OCT), electroretinography (ERG), histological, and transcriptional analyses were conducted in young and adult mice. Alterations in gene expression of late-born cells were observed as early as postnatal day 7 (P7), resulting in impaired rod function, a significantly reduced number of rod bipolar cells and their associated function, and a decreased Muller glia population at adult age. These defects appear to be caused by a delay in differentiation/ incomplete maturation, as indicated by an enlarged progenitor/precursor population at young ages that persists into adulthood. Notably, an increased population of HuC/D+ amacrine cells was found. Luciferase assays led us to speculate that this increase may be due to the absence of Elavl3 suppression via RPC-miRNAs. This suggests that Dicer/miRNAs in late RPC/PCs are essential for the proper formation and maturation of late RPC progenies and may also play a role in regulating cell state. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/635135v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@9e0950org.highwire.dtl.DTLVardef@1757e2corg.highwire.dtl.DTLVardef@aeb5ecorg.highwire.dtl.DTLVardef@29accb_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary statementLate-retinal progenitor microRNAs are essential for proper postnatal retinogenesis and retinal function.
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