K252a, an inhibitor of Trk, disturbs pathfinding of hippocampal mossy fibers.
Hippocampal mossy fibers, which are the axons of dentate granule cells, are continuously generated owing to adult neurogenesis of granule cells. They extend exclusively into the stratum lucidum, a proximal layer of the CA3 pyramidal cells. We visualized the mossy fiber tracts by Timm histochemical staining and DiI labeling in the cultured hippocampal slices from newborn rats. The fibers were abnormally expanded when the slices were cultured in the presence of K252a, an inhibitor of the neurotrophin receptor Trk. Similar defasciculation was observed with an inhibitor of MEK, which is one of the signaling molecules downstream of Trk. This study suggests for the first time that Trk and the MEK pathway are required for mossy fiber pathfinding.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Makoto
M
Tamura
Ryuta
R
Koyama
Yuji
Y
Ikegaya
Norio
N
Matsuki
Maki K
MK
Yamada
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D002232:Carbocyanines; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D006651:Histocytochemistry; D026121:Indole Alkaloids; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000254:growth & development*; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000037:antagonists & inhibitors*
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D002232:Carbocyanines; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; C024286:3,3'-dioctadecylindocarbocyanine; C049985:staurosporine aglycone; D020917:Receptor, trkA; D020930:MAP Kinase Kinase Kinases