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Xiaohuan Xia, Iqbal Ahmad; Lin28a regulates retinal neurogliogenesis and confers ectopic neural potential on Müller glia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4203.
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© ARVO (1962-2015); The Authors (2016-present)
During the development of central nervous system (CNS), neurogenesis precedes gliogenesis. However, the mechanism underlying this temporal transition is poorly understood. Although most of studies on CNS showed the effect of Lin28 in regulating the self-renewal of neural stem cells, observations in P19 cells suggested that Lin28 might be involved in regulating the temporal generation of neurons and glia (Balzer et al., 2010, Development. 137:891). Here, we have examined the role of Lin28a in retinal neurogliogenesis to understand the apparent lack of neurogenic potential in mammalian Müller glia (MG).
Lentivirus/retrovirus-mediated gain-of-function (GOF) and loss-of-function (LOF) perturbations were carried out in the late retinal progenitor cells (RPCs) (E18) in neurosphere culture, retinal explant culture, and in vivo (PN1-PN3) to demonstrate the influence of Lin28a on the generation of late born neurons (rod photoreceptors and bipolar cells) and MG. Lin28a LOF and GOF perturbations were carried out in the early RPCs (E14) and enriched MG, respectively, to demonstrate the influence of Lin28a on the generation and neurogenic potential of MG.
Lin28a LOF in late RPCs in all models studies significantly promoted differentiation of late born neurons and inhibited the generation of MG. In contrast, when Lin28a was knocked down in late RPCs, more MG and fewer late born neurons were generated, compared to controls. Interestingly, knockdown of Lin28a in early RPCs promoted their premature differentiation along glial lineage. When Lin28 was ectopically expressed in enriched MG, a subset of them acquired neuronal morphology and expressed neuronal markers, while decreasing the expression of glial markers.
Lin28a may regulate the timing of neuronal versus glial differentiation in the developing retina and represent a target for facilitating neurogenic properties in MG.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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