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.
journal_name
Neuronjournal_title
Neuronauthors
Ambrozkiewicz MC,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,doi
10.1016/j.neuron.2018.10.008subject
Has Abstractpub_date
2018-12-05 00:00:00pages
1097-1115.e15issue
5eissn
0896-6273issn
1097-4199pii
S0896-6273(18)30896-1journal_volume
100pub_type
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