Control of cortical neuron layering: lessons from mouse chimeras.
How is the activation of Reelin signalling within neurons translated into the layering of cortical neurons? To address this question, we made mouse chimeras to test the reciprocal effects of neurons possessing different genotypes but sharing a common cortical environment during development. In chimeras composed of wild-type and mutant neurons (for either Reelin, Dab1 or p35 genes), a common observation was the formation of a second set of cortical layers on top of an inverted mutant cortex. The secondary cortex was invariably layered in the correct order, and in Dab1 and p35 chimeras, they were principally composed of wild-type neurons. In contrast to these cell-autonomous effects, Reelin chimeras displayed non cell-autonomous effects. In these chimeras, only a small number of wild-type neurons were required to be present in order for a secondary cortex to be formed. Interestingly, the principal constituents of the secondary cortex are not wild-type but mutant neurons, suggesting non cell-autonomous signalling by low levels of Reelin. Overall, these results suggest that information for the generation of cortical layers is vested within neuroepithelial progenitors even before the first neurons have been born, but the guidance of successive generations of daughter neurons to their proper locations requires the activation of Reelin and p35.
Hammond
Vicki
V
Howard Florey Institute, The University of Melbourne, Parkville 3010, Victoria, Australia.
Britto
Joanne
J
So
Eva
E
Cate
Holly
H
Tan
Seong-Seng
SS
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000196:embryology*; D002678:Chimera / Q000196:embryology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C089495:neuronal Cdk5 activator (p25-p35); C000717128:Reln protein, mouse; D012697:Serine Endopeptidases