Time constraints and positional cues in the developing cerebellum regulate Purkinje cell placement in the cortical architecture.
To elucidate the mechanisms that regulate neuronal placement and integration in the cerebellar circuitry, we assessed the fate of Purkinje cells transplanted to embryonic, juvenile and adult hosts, asking how architectural changes of the developing cortex influence their anatomical incorporation. Donor Purkinje cells navigate through the host parenchyma either along their natural migratory pathway or following unusual routes. In the latter case, donor neurons fail to orientate correctly and to establish the cortico-nuclear projection. Purkinje cells that follow the physiological route achieve the typical orientation and connectivity, but end displaced in the molecular layer if their arrival in the recipient cortex is delayed. Navigation routes and final settling of donor neurons vary with host age, depending on the ontogenetic construction of cortical layering, and particularly on the maturation of granule cells. The migratory behavior and homing of transplanted Purkinje cells is modified after external granular layer ablation, or neutralization of reelin signaling produced by granule cells. Therefore, although the cerebellar milieu remains receptive for Purkinje cells even after the end of development, correct placement of donor neurons depends on the timing of their migration, related to cerebellar developmental dynamics and granule cell layering.
Carletti
Barbara
B
Department of Neuroscience, Rita Levi Montalcini Centre for Brain Repair, National Institute of Neuroscience, University of Turin, Italy.
Williams
Ian Martin
IM
Leto
Ketty
K
Nakajima
Kazunori
K
Magrassi
Lorenzo
L
Rossi
Ferdinando
F
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D013997:Time Factors
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases