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  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-Lazaro, A., et al. (2018). Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140. Neuron, 100(5), 1097-1115. doi:10.1016/j.neuron.2018.10.008.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-B1A3-D Version Permalink: http://hdl.handle.net/21.11116/0000-0003-1E36-0
Genre: Journal Article

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 Creators:
Ambrozkiewicz, M. C., Author
Schwark, M., Author
Kishimoto-Suga, M., Author
Borisova, E., Author
Hori, K., Author
Salazar-Lazaro, A., Author
Rusanova, A., Author
Altas, B., Author
Piepkorn, L., Author
Bessa, P., Author
Schaub, T., Author
Zhang, X., Author
Rabe, T.1, Author              
Ripamonti, S., Author
Rosario, M., Author
Akiyama, H., Author
Jahn, O., Author
Kobayashi, T., Author
Hoshino, M., Author
Tarabykin, V., Author
Kawabe, H., Author more..
Affiliations:
1Research Group of Molecular Cell Differentiation, MPI for biophysical chemistry, Max Planck Society, ou_578588              

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 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.

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Language(s): eng - English
 Dates: 2018-11-012018-12-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.neuron.2018.10.008
 Degree: -

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Title: Neuron
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 100 (5) Sequence Number: - Start / End Page: 1097 - 1115 Identifier: -