A study on the development of the cerebral neocortex using mice with perturbations on the subplate neurons

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The subplate is a layer that develops earliest in the neocortex. Neurones in the layer (SP neurones) are considered to play pioneering roles for neurones in the cortical plates, which develop later. In order to elucidated these roles, I planed to produce model mice devoid of SP neurones. The early proximal promoter (EPP), a part of golli promoter contained in myelin basic protein gene, was found to drive a strong and sustained expression of proteins in SP neurones. Reverse caspase-3 was known to elicit an immediate death in the cells that express it. I planed to delete the subplate by delivering reverse caspase-3 under the control of EPP. It was found, however, that even diminution of number of SP neurones caused extensive defects of the brain and premature death of mice to make developmental analyzes difficult. I then tried to perturb specific functions of SP neurones played by their radial neurites. Constitutively active calcineurin, which is constructed by deletion of the calcium-ca … More lmodulin regulatory domain of the native calcineurin, was found to suppress extension of neurites. I am trying to analyze changes of SP neurones and their effects in the mice that express constitutively active calcineurin under the control of EPP.In order to compare with the mice whose SP neurones are perturbed, I analyzed neocortical development of transgenic mice expressing excess interleukin-9, in which, I have found, the development of SP neurones is enhanced. A study of discrimination tasks was achieved with the transgenic mice by training them to touch a panel instead of to push lever in response to a light stimulus. The transgenic mice showed a lower achievement level than control mice with the same genetic background.A novel monoclonal antibody 4E1, which we have produced, was found to have a specific immunoreactivity in amoeboid microglia. Strong immunoreactivity was found on microglia attached to migrating neurones in the subplate, intermediate zone and subventricular zone. This suggests that microglia participates in neuronal migration or extension of neurites. Less