MicroRNA Profile of the Developing Mouse Retina

Abstract

Purpose. MicroRNAs (miRNAs) are short, noncoding transcripts that negatively regulate gene expression. They are implicated in diverse cellular processes. The purpose of this study was to obtain a global expression profile of miRNAs in the developing retina and identify differences in miRNA expression between adult rod and cone photoreceptors. Methods. Locked nucleic acid (LNA) microarrays were used to investigate the miRNA transcriptome of the developing mouse retina and brain. Real-time PCR was used to validate the array findings. Laser capture microdissection was used to determine the miRNA spatial pattern of expression. Results. One hundred thirty-eight miRNAs were expressed at at least one of the investigated time points. Several miRNAs showed significant changes in expression between embryonic day 15 and adult age in both retina and brain. Cluster analysis identified subgroups of miRNAs showing defined expression profiles. Globally, correlation of expression was higher, with increasing sequence similarity of the mature miRNAs. The miRNAs with identical seed sequences exhibited highly correlated expression profiles. The co-expression of selected host gene and intronic miRNA pairs was confirmed in adult retina. In some cases, expression profiles of miRNAs showed weak correlation with those of their host transcripts, suggesting posttranscriptional regulation of miRNAs during development. In addition, the miRNA transcriptome of rod- and cone-dominant retinas showed only minor differences, and no miRNAs specific for either cell-type were identified. Conclusions. Global expression profiling revealed dozens of miRNAs with significant expression changes in the developing retina. Precise patterns of expression of miRNAs suggest their specific roles in development.

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

“…The developmental increase in expression of miR-9, miR125b, and let-7 family members that we observe in the retinal progenitors confirms and extends earlier analyses of retinal miRNAs (31)(32)(33)(34)(35)(36). The most recent comprehensive microarray and in situ analyses (31,35) show that miR-9, miR-125, and several members of the let-7 family (including let-7a, -b, -c, -d, -e, -f, -g, and -i) are expressed in the retina and increase over the developmental period that we have analyzed.…”

“…The most recent comprehensive microarray and in situ analyses (31,35) show that miR-9, miR-125, and several members of the let-7 family (including let-7a, -b, -c, -d, -e, -f, -g, and -i) are expressed in the retina and increase over the developmental period that we have analyzed. Moreover, previous in situ localization studies have demonstrated that there is widespread expression of let-7 family members in all retinal layers from E16.5 to adulthood (ref.…”

MicroRNA 329 Suppresses Angiogenesis by Targeting CD146

“…Oxygen-induced retinopathy has long served as a useful model for studying pathological angiogenesis (36). Although recent studies reported the expression profiles of many miRNAs in the normal retinas of mice, including miR-329, its targets and function were unknown (44,45). Moreover, only a few miRNAs have been identified to regulate OIR (46,47).…”

Roles for Dicer1 in the patterning and differentiation of the optic cup neuroepithelium

“…Harfe et al, 2005;Harris et al, 2006). Dozens of miRNAs have been detected in the mouse eye, some showing dynamic expression patterns during ocular development (Hackler et al, 2010;Xu et al, 2007). Targeting of Dicer1 in Xenopus embryos revealed its importance for cell-cycle exit, survival and differentiation timing of retinal cells (Decembrini et al, 2008).…”