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channels. Indeed, gap junctions were first discovered in heart muscle cells
and neurons because of the intercellular electrical transmission of these cells
( Furshpan and Potter, 1957; Weidmann, 1952 ). In these excitable cells, elec-
trical coupling through gap junctions provides increased synaptic transmis-
sion speed and the ability to synchronize the contractions of heart muscle
cells for coordinated electromechanical output. In addition to neurons
and cardiac muscles, gap junctions are found joining almost all solid animal
tissues, with the possible exceptions of adult skeletal muscle and cells typi-
cally not in contact with neighboring cells, such as blood cells ( Sperelakis and
Ramasamy, 2005 ). In nonexcitable cells, gap junctions help control nutrient
and signaling molecule distribution across
tissues
( Goodenough and
Paul, 2009 ).
3. CELL JUNCTIONS IN DEVELOPMENT
3.1. Overview
Embryos during early development have unique advantages that make them
valuable models for studying cell junctions. The first differentiated cell type
formed in mammal embryogenesis is a trophectoderm epithelium, a single-
layered tissue dominated by intercellular adhesions. This initial epithelium
comprises all major cell-cell junctions, each performing fundamental roles
in the developing embryo ( Eckert and Fleming, 2008; Larue et al., 1994 ).
Development of any multicellular organism is likely impossible without
precisely regulated cell-cell adhesion. Many developmental processes,
including embryonic compaction and cell fate determination, as well as
tissue morphogenesis and organogenesis post-early development, are guided
by a dynamic balance dependent on intercellular junctions, mechanical
stresses, and the cytoskeleton ( Jamora and Fuchs, 2002; Stepniak et al.,
2009 ). Additionally, there is little evidence that early epithelial
trophectoderm development engages extracellular matrix/integrin compo-
nents, other than in making the basement membrane, suggesting that cell
junctions may dominate during this period ( Bowen and Hunt, 2000;
Sueoka et al., 1997 ). Thus, by virtue of limited cell-ECM interactions,
the epithelial trophectoderm is an ideal model for investigating cellular
interaction-mediated developmental mechanisms.
Though still not entirely established, it is widely thought that the timing
of cell junction assembly in the preimplantation embryo is precisely con-
trolled ( Green et al., 2010 ). E-cadherin-based junctional signaling, which
occurs early in development, is required for embryonic compaction and
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