with a blockade of neuronal differentiation, miR-34a overexpression delayed the expression of the presynaptic and postsynaptic neuronal markers SYP, SYN1 and PSD-95 over the neurodevelopmental time course (Figures 3D-E). In agreement with these findings, a similar phenotype was observed in 2 weeks differentiated neurons from the BD line in which miR-34a expression was previously found to be upregulated (Figure 3D). Of note, SYP and CACNB3 are not expressed at this stage of differentiation (Figure 3D). Moreover, ectopic overexpression of miR-34a and inhibition of endogenous miR-34a using an anti-miR-34a strategy altered neuronal morphology (Figures 3F-H) resulting in a significant reduction or increase of dendritic length and branch number when miR-34a expression was increased or decreased, respectively (Figures 3G-H). These results are highly reminiscent of those observed by Agostini et al.26 in mouse cortical neurons revealing with this first demonstration in human neurons of an evolutionarily conserved function of miR-34a in the regulation of dendritic morphology.
