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| 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., Schwark, M., Kishimoto-Suga, M., Borisova, E., Hori, K., Salazar-Lázaro, A., Rusanova, A., Altas, B., Piepkorn, L., Bessa, P., Schaub, T., Zhang, X., Rabe, T., Ripamonti, S., Rosário, M., Akiyama, H., Jahn, O., Kobayashi, T., Hoshino, M., 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 |
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