title: Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth.
abstract: Semaphorin 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.
authors.affiliation: Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794-5230, USA. maya.shelly@stonybrook.edu
authors.forename: Maya
authors.initials: M
authors.lastname: Shelly
authors.forename: Laura
authors.initials: L
authors.lastname: Cancedda
authors.forename: Byung Kook
authors.initials: BK
authors.lastname: Lim
authors.forename: Andrei T
authors.initials: AT
authors.lastname: Popescu
authors.forename: Pei-lin
authors.initials: PL
authors.lastname: Cheng
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Gao
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D040121:Semaphorin-3A / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D039942:Neuropilin-1; D000242:Cyclic AMP; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000091162:AMP-Activated Protein Kinase Kinases; D006152:Cyclic GMP