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. With in situ hybridization 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 by in situ hybridization. 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 downregulated. 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.

α3β1 integrin modulates neuronal migration and placement during early stages of cerebral cortical development

“…α3 integrin can influence oriented neuronal movement in multiple ways. For example, α3 integrins can influence neuronal response to cues such as fibronectin (Hodivala-Dilke et al, 1998), which is present along the radial glial migratory routes in cerebral cortex (Pearlman and Sheppard, 1996;Sheppard et al, 1991;Sheppard et al, 1995;Stettler and Galileo, 2004). Consistent with this possibility is the observation that α3 integrin mutant embryonic cortical neurons display enhanced (+62±0.06%) adhesion to fibronectin substrate in vitro (see Fig.…”

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an αvIntegrin/Myelin Proteolipid Protein Complex

“…Fibronectin is produced in the developing brain by both radial glia and neurons. It is initially expressed by radial glia, which align the fibronectin in radial stripes, presumably as part of the guidance role that radial glia provide in the developing brain (Sheppard et al, 1995;Stettler and Galileo, 2004). It is subsequently found in the outer cortical layers, produced primarily by neurons migrating within the cortex (Sheppard et al, 1995).…”

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

“…Although FN is not present at high levels in adult brain, it is known to support survival and migration of neural cells during development (Chun and Shatz, 1988;Pearlman and Sheppard, 1996;Sheppard et al, 1995) and in transplants (Tate et al, 2002). In addition, FN is upregulated after cerebral injury (Egan and Vijayan, 1991;Tate et al, 2007), in epileptic seizures (Hoffman et al, 1998), and it also ameliorates effects of ischemic stroke (Sakai et al, 2001).…”