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Cereb Cortex ; 24(11): 2835-47, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23749873

RESUMO

Malformations of cortical development can arise when projection neurons generated in the germinal zones fail to migrate properly into the cortical plate. This process is critically dependent on the Reelin glycoprotein, which when absent leads to an inversion of cortical layers and blurring of borders. Reelin has other functions including supporting neuron migration and maintaining their trajectories; however, the precise role on glial fiber-dependent or -independent migration of neurons remains controversial. In this study, we wish to test the hypothesis that migrating cortical neurons at different levels of the cortical wall have differential responses to Reelin. We exposed neurons migrating across the cortical wall to exogenous Reelin and monitored their migratory behavior using time-lapse imaging. Our results show that, in the germinal zones, exogenous Reelin retarded neuron migration and altered their trajectories. This behavior is in contrast to the response of neurons located in the intermediate zone (IZ), possibly because Reelin receptors are not expressed in this zone. In the reeler cortex, Reelin receptors are expressed in the IZ and exposure to exogenous Reelin was able to rescue the migratory defect. These studies demonstrate that migrating neurons have nonequivalent responses to Reelin depending on their location within the cortical wall.


Assuntos
Moléculas de Adesão Celular Neuronais/farmacologia , Movimento Celular/efeitos dos fármacos , Córtex Cerebral/citologia , Proteínas da Matriz Extracelular/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Serina Endopeptidases/farmacologia , Proteínas Adaptadoras de Transporte Vesicular/deficiência , Proteínas Adaptadoras de Transporte Vesicular/genética , Fatores Etários , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Análise de Variância , Animais , Linhagem Celular Transformada , Movimento Celular/genética , Eletroporação , Embrião de Mamíferos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Técnicas In Vitro , Camundongos , Camundongos Mutantes Neurológicos , Microscopia Confocal , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Transfecção
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