Isolation and community: A review of the role of gap-junctional communication in embryonic patterning

Gap junctions are specialized channels formed between the membranes of two adjacent cells. They permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Gap junction states can be regulated at many levels by factors such as membrane voltage, pH, phosphorylation state, and biochemical signals. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology, as well as in tumor progression. However, arguably the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development. This review summarizes the current knowledge of how GJC controls various aspects of embryonic morphogenesis in both vertebrate and invertebrate systems. Modern molecular embryology approaches have complemented biophysical and ultrastructural data, and we are beginning to unravel the patterning roles of GJC in embryonic events such as the patterning of the embryonic left-right axis, as well as the morphogenesis of the heart and limb. Proteins from the Connexin (Cx) gene family, as well as innexins and ductin, are now beginning to be understood as the basis for GJC underlying important embryonic patterning events.