title: Congruence of vascular network remodeling and neuronal dispersion in the hippocampus of reelin-deficient mice.
abstract: In the hippocampus, neurons and fiber projections are strictly organized in layers and supplied with oxygen via a vascular network that also develops layer-specific characteristics in wild-type mice, as shown in the present study for the first time in a quantitative manner. By contrast, in the reeler mutant, well known for its neuronal migration defects due to the lack of the extracellular matrix protein reelin, emerging layer-specific characteristics of the vascular pattern were found to be remodeled during development of the dentate gyrus. Remarkably, in the first postnatal week, when a granule cell layer was still discernable in the reeler dentate gyrus, also the reeler vascular pattern resembled wild type. Thus, at postnatal day 6, unbranched microvessels traversed the granule cell layer and bifurcated when reaching the subgranular zone. Only after the first postnatal week vascular network remodeling in the reeler dentate gyrus became apparent, when the proportion of dispersed granule cells increased. Hence, vessel bifurcation frequency decreased in the maturing reeler dentate gyrus, but increased in wild type, resulting in significant differences (approx. 100%; p < 0.01) between adult wild type and reeler. Moreover, layer-specific vessel bifurcation frequencies disappeared in the maturing reeler dentate gyrus. Finally, a wild type-like vascular pattern was also found in the dentate gyrus of mice deficient for the reelin receptor very low density lipoprotein receptor (VLDLR), precluding a requirement of VLDLR for normal vascular pattern formation in the dentate gyrus. In sum, our findings show that vascular network remodeling in the reeler dentate gyrus is closely linked to the progression of granule cell dispersion.
authors.affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Lindhorst
authors.forename: Haymo
authors.initials: H
authors.lastname: Kurz
authors.forename: Mirjam
authors.initials: M
authors.lastname: Sibbe
authors.forename: Maurice
authors.initials: M
authors.lastname: Meseke
authors.forename: Eckart
authors.initials: E
authors.lastname: Förster
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000378:metabolism; D018891:Dentate Gyrus / Q000098:blood supply* / Q000166:cytology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases