REPRODUCTIONREVIEW Role of gap junctions during early embryo development

Gap junctional communication plays a central role in the maintenance of cellular homeostasis by allowing the passage of small molecules between adjacent cells. Gap junctions are composed of a family of proteins termed connexins. During preim-plantation development several connexin proteins are expressed and assembled into gap junctions in the plasma membrane at compaction but the functional significance of connexin diversity remains controversial. Although, many of the connexin genes have been disrupted using homologous recombination in embryonic stem cells to obtain unique phenotypes, none of these studies has demonstrated a specific role for connexins during preimplantation development in the null mutants. This review surveys evidence for the involvement of gap junctional communication during embryo development highlighting discrepancies in the literature. Although some evidence suggests that gap junctions may be dispensable during preimplantation development this is difficult to envisage particularly for the process of cavitation and the maintenance of homeostasis between the differen-tiated trophectoderm cells and the pluripotent inner cell mass cells of the blastocyst. Reproduction (2005) 129 129–135 Gap-junction structure Gap junctions maintain cellular homeostasis by allowing communication between adjacent cells. They span the plasma membrane of two adjacent cells (Makowski et al. 1977), with each cell contributing half the channel; a hemichannel, or connexon. A connexon from one cell docks in the extracellular space with a connexon from an opposing cell to form a complete gap-junction channel, allowing adjacent cells to be coupled (reviewed by Bruzzone et al. 1996a). Each connexon is a multimeric assembly of six proteins, termed connexins (Fig. 1). Con-nexons may be composed of the same type of connexin, termed homomeric, or contain multiple connexins, termed heteromeric connexons. The docking of two homomeric connexons composed of the same connexin protein yields a homotypic channel, whereas the oligomerization of two homomeric connexins composed of different connexins forms a heterotypic channel (Revel & Karnovsky 1967