CONNEXINS AND NEURAL DEVELOPMENT

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Developmental brain abnormalities are a major cause of mental retardation. Appropriate patterning is critical to development of the central nervous system. Compartments of cellular communication coordinated through gap junction channels may be critical for the determination of patterns and their stabilization. Our prior studies have suggested a possible mechanism for forming these compartments and their boundaries - the expression of gap junction subunit proteins (connexins, Cx) that have different permeability and regulatory properties and that modify (or inhibit) the properties of co-expressed connexins. We will evaluate the contributions of five connexins (CX36, CX45, CX56, CX43, and the newly discovered CX33.2) in the development of two regions of the nervous system (hindbrain and spinal cord). Connexin expression will be characterized by in situ hybridization and immunohistochemistry and related to domains of intercellular communication, patterning of gene expression, cell growth, apoptosis, and neuronal migration. The biochemical and functional properties of CX33.2 will be determined. Connexin gene expression and cellular coupling will be modified by gene electroporation, and the developmental consequences determined.