Developmental regulation of gap junctions and their role in mammary epithelial cell differentiation

Gap junctions play a critical role in the development and differentiation of many tissues. Formed by the joining of two connexons on opposing membranes of two cells, gap junctions permit passage of ions and small molecules. Six connexins (Cx) belonging to a family of closely related tetraspan transmembrane proteins form a connexon. Connexin expression peaks in lactation, and those identified in the gland, thus far, are Cx26, Cx30, Cx32, and Cx43. Cx43 associates with myoepithelial cells, while others associate with epithelial and ductular cells. In vitro, assembly of functional gap junctions appears to be essential for differentiation of mammary epithelial cells. However, the role of gap junction intercellular communication (GJIC) in differentiation and growth remains unclear. Recent evidence challenges the view that gap junctions are simply pore-forming proteins and suggests that cell adhesion-associated proteins interact with the cytosolic carboxy-terminus of connexins and participate in signaling events. The possible implications on mammary cell function are discussed.