January 27, 2021

Distinct temporal expression of GW182 in neurons regulates dendritic arborization

Precise development of the dendritic architecture is a critical determinant of mature neuronal circuitry. MicroRNA-mediated regulation of protein synthesis plays a crucial role in dendritic morphogenesis but the role of miRISC protein components in this process is less studied. Here, we show an important role of a core miRISC protein GW182 in the regulation of dendritic growth. We have identified a distinct brain region specific Spatio-temporal expression pattern of GW182 during rat postnatal development. We found that the window of peak GW182 expression coincides with the period of extensive dendritic growth, both in the hippocampus and cerebellum. Perturbation of GW182 function results in reduced dendritic growth in cultured hippocampal neurons during a specific temporal window. We found that GW182 affects dendritic growth by regulating global somato-dendritic translation, and consequently, affects the actin cytoskeletal arrangement in developing neurons. We identified LIMK1 as one of the key actin modulator candidates whose expression is regulated by GW182, in turn affecting dendritic arborization. Taken together, our data reveal a previously undescribed neurodevelopmental expression pattern of GW182 and its role in dendritic morphogenesis, through both translational control and actin cytoskeletal rearrangement.

 bioRxiv Subject Collection: Neuroscience

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