Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 192

3.3. Desmosomes
Also important to development are desmosomes, as demonstrated by studies
from both spontaneous and engineered mutations. Deletion of certain genes
encoding desmosomal proteins causes early embryonic lethality due to either
mechanical or signaling defects ( Thomason et al., 2010 ). Conditional abla-
tion of desmoplakin in the heart or null mutations of plakoglobin or
plakophilin yield animals with cardiac abnormalities and associated lethality
( Aberle et al., 1995; Garcia-Gras et al., 2006 ). Studies in desmoplakin-null
embryos demonstrated that impaired desmosomes significantly influence
embryonic tissue shape, suggesting desmosome assembly and its linkage to
intermediate filaments are crucial for proper development ( Gallicano
et al., 1998 ). Mutations in the desmosomal cadherins resulted in similar phe-
notypes. For example, loss of desmoglein 2 and desmoglein 3 results in the
loss of embryonic viability near implantation and diminished stem cell pro-
liferation, suggesting that these proteins are essential for development ( Den
et al., 2006; Eshkind et al., 2002 ).
3.4. Tight junctions
Tight junctional assembly is engaged by asymmetric exogenous cell contact
patterns and restricted to the outer trophectoderm layer due to the symmetry
of cell contact within the blastocyst ( Eckert et al., 2004; Kimber et al., 1982;
Schock and Perrimon, 2002 ). This expression pattern can be recapitulated
by immunosurgically isolating the inner cell masses, thus creating a new
“outer layer” which then upregulates tight junctional expression ( Eckert
et al., 2004, 2005 ). The importance of tight junctions for embryonic devel-
opment is demonstrated by their role in epithelial differentiation, since inhi-
bition of tight junction components causes defects in blastocoele
morphogenesis ( Kim et al., 2004; Sheth et al., 2000; Thomas et al.,
2004 ). Additionally, deficiency of the zona occludens, ZO-1 and ZO-2,
causes an embryonic lethal phenotype associated with defective yolk sac
angiogenesis and embryonic cell death ( Katsuno et al., 2008; Xu
et al., 2008 ).
3.5. Gap junctions
The precise role of connexins during formation and function of gap junc-
tions during development remains unresolved, although they are expressed
as early as the four-cell stage ( Hardy et al., 1996 ). Experimental approaches
similar to those deployed for studying the other classes of cell junctions were