Semaphorin3A accelerates neuronal polarity in vitro and in its absence the orientation of DRG neuronal polarity in vivo is distorted.
Axon guidance cues are critical for neuronal circuitry formation. Guidance molecules may repel or attract axons directly by effecting growth cone motility, or by impinging on neuronal polarity. In Semaphorin3A null mice, many axonal errors are detected, most prominently in DRG neurons. It has been generally assumed the repellent properties of Semaphorin3A are the cause of these erroneous axonal projections. Here we show that, in semaphorin3A-null mice, the initial trajectory of neurons in the DRG is abnormal, suggesting that Semaphorin3A may instruct neuronal polarity. In corroboration, in vitro Semaphorin3A dramatically increases neuronal polarization, as indicated by GSK3beta and Rac1 sub-cellular localization in DRG neurons. Polarization effects of Semaphorin3A are regulated by activated MAPK, as indicated by p-MAPK 42/44 polarization and the need for its activity for Rac1 and GSK3beta polarization. Taken together, our findings suggest that Semaphorin3A plays a role in the formation of neuronal polarity, in addition to its classic repellent role.
Lerman
Omer
O
The Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, The Hebrew University Faculty of Medicine, PO Box 12272, Jerusalem 91120, Israel.
Ben-Zvi
Ayal
A
Yagil
Zohar
Z
Behar
Oded
O
D000818:Animals; D001369:Axons / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003712:Dendrites / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D040121:Semaphorin-3A / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D004791:Enzyme Inhibitors; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D014404:Tubulin; D002392:Catechin; C045651:epigallocatechin gallate; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3