![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
| Item Type: | Article |
|---|---|
| Title: | Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140 |
| Creators Name: | Ambrozkiewicz, M.C. and Schwark, M. and Kishimoto-Suga, M. and Borisova, E. and Hori, K. and Salazar-Lázaro, A. and Rusanova, A. and Altas, B. and Piepkorn, L. and Bessa, P. and Schaub, T. and Zhang, X. and Rabe, T. and Ripamonti, S. and Rosário, M. and Akiyama, H. and Jahn, O. and Kobayashi, T. and Hoshino, M. and Tarabykin, V. and Kawabe, H. |
| Abstract: | The establishment of axon-dendrite polarity is fundamental for radial migration of neurons during cortex development of mammals. We demonstrate that the E3 ubiquitin ligases WW-Containing Proteins 1 and 2 (Wwp1 and Wwp2) are indispensable for proper polarization of developing neurons. We show that knockout of Wwp1 and Wwp2 results in defects in axon-dendrite polarity in pyramidal neurons, and their aberrant laminar cortical distribution. Knockout of miR-140, encoded in Wwp2 intron, engenders phenotypic changes analogous to those upon Wwp1 and Wwp2 deletion. Intriguingly, transcription of the Wwp1 and Wwp2/miR-140 loci in neurons is induced by the transcription factor Sox9. Finally, we provide evidence that miR-140 supervises the establishment of axon-dendrite polarity through repression of Fyn kinase mRNA. Our data delineate a novel regulatory pathway that involves Sox9-[Wwp1/Wwp2/miR-140]-Fyn required for axon specification, acquisition of pyramidal morphology, and proper laminar distribution of cortical neurons. |
| Keywords: | Neuronal Development, Axon Formation, Neuronal Migration, Neuronal Differentiation, Ubiquitin, Intronic microRNA, Host Gene, Animals, Mice |
| Source: | Neuron |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Volume: | 100 |
| Number: | 5 |
| Page Range: | 1097-1115 |
| Date: | 5 December 2018 |
| Official Publication: | https://doi.org/10.1016/j.neuron.2018.10.008 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
