MIR-138 PROMOTES THE MIGRATION OF CULTURED CHICKEN EMBRYONIC HYPOTHALAMIC CELLS BY TARGETING REELIN

Neuronal network remodeling during critical periods of sensory development might be accompanied by alterations in hypothalamic cell populations. MicroRNAs play a central role in regulating neuronal function, including neural stem cell proliferation, and neuronal migration, maturation and integration into viable circuits by modulating different mRNA targets. Here we investigated the role of miR-138 in cell proliferation and migration in a neuron-enriched hypothalamic cell culture prepared from chicks on embryonic day 16. Ectopic expression of miR-138 enhanced hypothalamic cell migration, but did not affect cell proliferation. As a potential mechanism for miR-138's effect on cell migration, we investigated reelin (Rein) as a direct target of miR-138. Luciferase reporter assay and Ago2-immunoprecipitation experiments confirmed direct binding of miR-138 to the Rein 3'-untranslated region. Ectopic miR-138 abolished Rein levels in hypothalamic cells and enhanced their migration, similar to Rein-antisense DNA. Furthermore, inhibition of Rein expression by miR-138 led to decreased phosphorylation level of the key component of Rein-regulated signaling cascades, Disabled 1. These findings describe miR-138 as a novel regulator of hypothalamic cell migration, acting at least in part via inhibition of Rein expression and leading to the inactivation of Rein signals. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.