Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice.
We have studied the organization and cellular differentiation of dentate granule cells and their axons, the mossy fibers, in reeler mutant mice lacking reelin and in mutants lacking the reelin receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). We show that granule cells in reeler mice do not form a densely packed granular layer, but are loosely distributed throughout the hilar region. Immunolabeling for calbindin and calretinin revealed that the sharp border between dentate granule cells and hilar mossy cells is completely lost in reeler mice. ApoER2/VLDLR double-knockout mice copy the reeler phenotype. Mice deficient only in VLDLR showed minor alterations of dentate organization; migration defects were more prominent in ApoER2 knockout mice. Tracing of the mossy fibers with Phaseolus vulgaris leukoagglutinin and calbindin immunolabeling revealed an irregular broad projection in reeler mice and ApoER2/VLDLR double knockouts, likely caused by the irregular wide distribution of granule cell somata. Mutants lacking only one of the lipoprotein receptors showed only minor changes in the mossy fiber projection. In all mutants, mossy fibers respected the CA3-CA1 border. Retrograde labeling with DiI showed that malpositioned granule cells also projected as normal to the CA3 region. These results indicate that ( 1 ) reelin signaling via ApoER2 and VLDLR is required for the normal positioning of dentate granule cells and (2) the reelin signaling pathway is not involved in pathfinding and target recognition of granule cell axons.
Drakew
Alexander
A
Institute of Anatomy, University of Freiburg, Albertstrasse 17, Freiburg, D-79104, Germany.
Deller
Thomas
T
Heimrich
Bernd
B
Gebhardt
Carl
C
Del Turco
Domenico
D
Tielsch
Albrecht
A
Förster
Eckart
E
Herz
Joachim
J
Frotscher
Michael
M
D000818:Animals; D002465:Cell Movement; D003712:Dendrites / Q000473:pathology; D018891:Dentate Gyrus / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D015335:Molecular Probes; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D009421:Nervous System Malformations / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D017966:Pyramidal Cells / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000172:deficiency* / Q000235:genetics; D000091042:Reelin Protein
D026502:LDL-Receptor Related Proteins; D015335:Molecular Probes; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse