Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes after entorhino-hippocampal axotomy.
We studied the changes in the distribution of a specific variant of Semaphorin Y/6C (Sema6C) in mouse forebrain after axotomy of the entorhino-hippocampal perforant pathway. We found this isoform to be widely expressed during development, remaining in the adult and showing variations in distribution when the perforant pathway was axotomized. These changes were detected in both the hippocampal and entorhinal cortices. Sema6C1 immunoreactivity (IR) was high in the stratum radiatum of the hippocampus proper and the inner molecular layer of the dentate gyrus; the entorhinal cortex showed Sema6C1 IR in both cell bodies and in fibers of the II/III and V/VI layers. In axotomized animals, the IR of the ipsilateral, but not the contralateral, hemisphere showed that IR had moved into the stratum lacunosum-moleculare, the medial molecular layer of the dentate gyrus and the fibers, but not the cell bodies, of the entorhinal cortex. These results were not reproduced after lateral axotomy of the fimbria fornix, indicating a specific role for Sema6C variants in the generation and/or stability of entorhino-hippocampal synapses. Growth cone collapse of entorhinal and pyramidal neurons, as well as activation of glycogen synthase kinase-3 (GSK-3) through depletion of the inactive pool, induced by diffusible Sema6C1 further supports this view.
Burgaya
Ferran
F
Institute for Research in Biomedicine (IRB) and Cell Biology Department, Faculty of Biology, University of Barcelona, Barcelona, Spain. fburgaya@pcb.ub.es
Fontana
Xavier
X
Martínez
Albert
A
Montolio
Marisol
M
Mingorance
Ana
A
Simó
Sergi
S
del Río
José Antonio
JA
Soriano
Eduardo
E
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019771:Axotomy / Q000379:methods; D019556:COS Cells; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian; D018728:Entorhinal Cortex / Q000166:cytology* / Q000378:metabolism; D007839:Functional Laterality; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019580:Perforant Pathway / Q000378:metabolism*; D039961:Semaphorins / Q000276:immunology / Q000502:physiology*; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection / Q000379:methods
D000906:Antibodies; C504199:Sema6c protein, mouse; D039961:Semaphorins; D038362:Glycogen Synthase Kinase 3