Neuronal Production of Fibronectin in the Cerebral Cortex during Migration and Layer Formation Is Unique to Specific Cortical Domains

Abstract

The distribution of fibronectin (FN) changes rapidly during early development of the cerebral cortex, but its cellular source is not known. Within situhybridization we find two spatially and temporally distinct periods of FN mRNA expression in the embryonic and early postnatal cortex of the mouse. Before and during formation of the preplate by the first postmitotic neurons, FN mRNA levels are high throughout the telencephalic vesicle, deep in the neuroepithelial proliferative zone that contains dividing cells and the cell bodies of radial glia; expression in the cortical proliferative zone is limited to the period of neurogenesis. Just after the cortical plate is formed within the preplate, FN mRNA is expressed in the intermediate zone, which contains migrating neurons, and in the cortical plate, where neurons migrate past their predecessors to form layers. Brefeldin A treatment of an organotypic slice preparation demonstrates FN production in the intermediate zone and cortical plate, in locations that correspond exactly to the distribution of FN mRNA byin situhybridization. FN-producing cells immunolabel with neuron-specific markers; in the intermediate zone and lower cortical plate they have morphological features characteristic of migrating neurons and are closely apposed to radial glia. FN mRNA expression and protein production continue in neurons of the cortical plate through the period of layer formation and then are down-regulated. Examination of dissociated cortical cells by laser confocal microscopy confirms that FN accumulation after brefeldin A treatment is intracellular in neurons as well as in glia. Neuroepithelial expression of FN mRNA takes place throughout the telencephalon; FN produced by neurons is restricted to cells migrating toward and into specific cortical domains that include neocortex, insular and perirhinal cortex, and subiculum. Thus FN may be involved initially in supporting the cell division and fate determination that takes place in the neuroepithelium; later production by migrating neurons may play a role in the selection of radial glial pathways that lead to specific cortical regions, and in interactions between neurons as they form cortical layers within these regions.