• Maya Shelly, Laura Cancedda, Byung Kook Lim, Andrei T Popescu, Pei-lin Cheng, Hongfeng Gao, and Mu-ming Poo.
• Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794-5230, USA. maya.shelly@stonybrook.edu
• Neuron. 2011 Aug 11;71(3):433-46.

AbstractSemaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.Copyright © 2011 Elsevier Inc. All rights reserved.

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