K252a, an inhibitor of Trk, disturbs pathfinding of hippocampal mossy fibers.
Tamura M, Koyama R, Ikegaya Y, Matsuki N, Yamada MK.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences,
The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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.
Publication Types:
Research Support, Non-U.S. Gov't
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