Molecular mechanisms of lamina-specific neural circuit formation in the neocortex

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The cerebral cortex is composed of six cell layered structure, by which neural connections are established. As such laminar structure is present in not only the cerebral cortex but also other central nervous systems, it is thought to be a principle for neural circuit formation. To date, developmental studies in vivo and in vitro studies including ours (Yamamoto et al, 1989,1992,1995,1997) have demonstrated that each layer cells have specific target recognition mechanisms to produce afferent and efferent connections. Moreover, the mechanisms are regulated by the molecules that are expressed in a lamina-specific fashion (Yamamoto et al, 2000a,b). However, the presence and function of these lamina-specific molecules were not almost unknown.In this study, we attempted to identify these lamina-specific molecules, and to reveal the involvement of them in cortical circuit formation. To do that, a subtraction cDNA library was constructed by extracting RNAs from each layer, and were applied to screening lamina-specific genes. As a result, several genes which code transcription factors and cell surface molecules were identified as layer 4 or layer 5-specific molecules. Moreover, a lamina-specific molecule, which belongs to cadherin family, was obtained by using monoclonal antibody technique. We suggested that these lamina-specific genes may be involved in cell type specification and cortical circuit formation by analyzing developmental expression patterns and relation between gene expression and cell types.