Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140

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.; Kawabe, H.

Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140

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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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