Abstract
Purpose:
The retina is built by a sequential production of different types of neurons and glia from a common multipotent progenitor; however, the molecular mechanisms that change the competence of the retinal progenitors over time remains unclear. We examined the role of microRNAs (miRNAs) and some of their target genes to gain new insights into the regulation of developmental timing in the retina
Methods:
We performed miRNA microarrays to identify miRNAs expression profiles during retinal development. Positive targets were confirmed by RT-qPCR and sensor-based analyses. We also tested the effect of miRNA overexpression by miRNA mimic electroporation in wild type and Dicer conditional knock-out (Dicer-CKO) retinal explants
Results:
We found that the stage-specific expression of miR-125, Let-7 and miR-9 negatively regulates the level of Protogenin (Prtg), and Lin28. Experimentally increasing the expression of these miRNAs at early stages of retinogenesis causes precocious development into cell types normally generated later in development. Conversely, experimental overexpression of Prtg or Lin28 at later stages of retinal development is sufficient to restore competence to generate early cell types
Conclusions:
We identified specific late-progenitor miRNAs and some of the target genes that control a developmental transition in progenitor competence.
Keywords: 698 retinal development •
688 retina •
500 differentiation