miR‐181a/b control the assembly of visual circuitry by regulating retinal axon specification and growth

Abstract

Connectivity and function of neuronal circuitry require the correct specification and growth of axons and dendrites. Here, we identify the microRNAs miR‐181a and miR‐181b as key regulators of retinal axon specification and growth. Loss of miR‐181a/b in medaka fish (Oryzias latipes) failed to consolidate amacrine cell processes into axons and delayed the growth of retinal ganglion cell (RGC) axons. These alterations were accompanied by defects in visual connectivity and function. We demonstrated that miR‐181a/b exert these actions through negative modulation of MAPK/ERK signaling that in turn leads to RhoA reduction and proper neuritogenesis in both amacrine cells and RGCs via local cytoskeletal rearrangement. Our results identify a new pathway for axon specification and growth unraveling a crucial role of miR‐181a/b in the proper establishment of visual system connectivity and function. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1252–1267, 2015

Electroacupuncture enhances rehabilitation through miR-181b targeting PirB after ischemic stroke

“…One possible explanation for these findings is that miR-181b increased pirb mRNA and PirB protein expression to regulate the expression of downstream signaling molecules, such as RhoA and GAP43. These results are consistent with those of the above in vivo study, in addition to a previous report demonstrating that PirB inhibition promotes the regeneration of hypoxic-ischemic-damaged axons and that this inhibitory signal may be transduced via the Rho-ROCK signaling pathway2941. Moreover, GAP43 is another downstream molecule of PirB that facilitates axonal sprouting and outgrowth16.…”

“…In particular, the relevance of miR-181b function to the organization of neural connections has been reported and identified. MiR-181b, a member of the miR-181 family, is expressed at intriguingly high levels in the retina and brain areas associated with motor function29. Furthermore, increasing evidence shows that miR-181b governs axon specification and growth by regulating its target signaling molecules and plays an important role in the organization of neural connections2941.…”

“…MiR-181b, a member of the miR-181 family, is expressed at intriguingly high levels in the retina and brain areas associated with motor function29. Furthermore, increasing evidence shows that miR-181b governs axon specification and growth by regulating its target signaling molecules and plays an important role in the organization of neural connections2941. However, the role of miR-181b in the ischemic penumbra in association with EA treatment for stroke remains to be elucidated.…”

“…The miRNAs are a class of endogenous, short (18 to 25 nucleotides) non-coding RNAs that bind to the 3′ untranslated regions (UTRs) of target mRNAs by complementary base pairing and prevent translation or destabilize the mRNAs to mediate their degradation or inhibit their translation2526. The miRNAs can be activated in response to neuronal activity, and therefore, they offer a highly effective means of and play crucial roles in controlling the expression of proteins involved in both the developing and mature brain, specifically during neuronal differentiation2728, axon regeneration29 and synaptic plasticity30. Thus, among the miRNAs with high levels of expression in the brain, those that regulate axon growth and target pirb mRNA in response to EA treatment for ischemic stroke need to be further explored.…”

miR‐181a/b downregulation exerts a protective action on mitochondrial disease models

“…Source data are available online for this figure. ª 2019 The Authors EMBO Molecular Medicine 11: e8734 | 2019 cox7B-MO) showed a severe microphthalmic and microcephalic phenotype due to increased cell death in the CNS (Indrieri et al, 2012(Indrieri et al, , 2013. In medaka, the mature forms of miR-181a and miR-181b are perfectly conserved with respect to their mammalian counterparts, in terms of both sequence identity (100%) and pattern of expression in the retina and brain (Carrella et al, 2015). We found that MO-mediated silencing of miR-181a/b in medaka leads to increased levels of the majority of targets involved in mitochondrial biogenesis and function, and in autophagy ( Fig EV2).…”