Cellular and Molecular Neurobiology
Author: Paula Gonzalez | Email: pgonzalez@iib.unsam.edu.ar
Paula M. González 1°, Rodolfo N. Sanchez Iazurlo 1°, Paula A. Aguirre 1°, Barbara Di Marco 3°, Julieta Alfonso 3°, Juan Pablo Fededa 1°
1° Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
2° Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín.
3° 3.Department of Clinical Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Emerging evidence suggests that microRNAs, critical post-transcriptional regulators of mRNA translation and stability, plays a crucial role in dendritic and synaptic development.
Here, we investigated the role of miR-191, a microRNA implicated in neurodegenerative diseases that is expressed in the murine brain cortex starting from peak cortical neurogenesis.
To elucidate the role of miR-191-5p function, we generated a novel approach using the CRISPR/Cas9 system delivered via intra-ventricular injections of the pan-neuronal PHP.eB adeno-associated virus (AAV), to deplete miR-191-5p in the early postnatal mice brain by editing the dicer processing bulge site.
Using Golgi-Cox staining coupled with confocal microscopy to assess the morphology of cortical interneurons by Sholl analysis, we found that depletion of miR-191-5p significantly shortened the average length of neuronal processes and reduced the total surface area of the dendritic tree. Additionally, cortical neurons exhibited decreased overall complexity under miR-191-5p depletion, which is consistent with a role for miR-191-5p in dendritic development. Tracing the processes of in vitro miR-191-5p depleted vs control N2A cells showed similar results.
Overall, this data suggests that miR-191-5p act as a positive regulator of neuronal branching during brain development. Further experimentation could unravel the regulatory mechanisms governing the observed phenotypes in vivo.