Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 191

the subsequent formation of a trophectodermal epithelium ( Larue et al.,
1994; Riethmacher et al., 1995; Torres et al., 1997 ). During compaction
(at around the eight-cell stage), loosely adherent spherical blastomeres
flatten, maximizing cell-cell contacts when the biogenesis of adherens junc-
tions, tight junctions, and gap junctions begins. Molecularly and morpho-
logically, the assembly of tight junctions displays a gradual process. In
contrast, the assembly of desmosomes begins when the embryo initiates
blastocoele formation, near the time of establishment of epithelial polarity
(32-cell stage) ( Ducibella et al., 1975; Fleming et al., 1991 ). Furthermore,
accumulating evidence suggests that cell junctions' dual roles in both struc-
ture and signaling may provide the means to integrate changes in morphol-
ogy and gene expression during development ( Jamora and Fuchs, 2002;
McCrea et al., 2009 ). Junctional proteins may facilitate intercellular signaling
pathways and eventually influence nuclear transcription, perhaps via esta-
blishing biochemical gradients or exchanging signaling molecules ( Wang
et al., 2001 ).
3.2. Adherens junctions
Adherens junctions are actively involved in both epithelial-mesenchymal
transition (EMT), a biological process characterized by dramatic loss of
cell-cell adhesion and reduction of E-cadherin expression, as well as the
reverse process of mesenchymal-epithelial transition (MET) ( Baum et al.,
2008; Yang and Weinberg, 2008 ). The cadherin-catenin network and asso-
ciated proteins are involved in major mitotic, differentiation, and apoptotic
signaling networks ( Cavey and Lecuit, 2009 ). Thus, alterations of adherens
junctions expression often lead to major developmental defects ( Stepniak
et al., 2009 ). Notably, many key proteins, such as E- or VE-cadherin, are
embryonic lethal when knocked out ( Carmeliet et al., 1999; Larue et al.,
1994 ). Loss-of-function and gain-of-function experiments revealed critical
roles for E-cadherin, N-cadherin, a -catenin, b -catenins, and p120-catenin
in early embryonic patterning. For example, numerous studies demonstrated
the involvement of E-cadherin in regulation of RTK signaling, N-cadherin in
FGF receptor signaling, a -catenin in RTK and Hedgehog signaling,
b -catenin in canonical Wnt signaling, and p120-catenin in RhoA, NF- k B,
and MAPK signaling pathways ( Bierkamp et al., 1996; Charpentier et al.,
2000; Huber, 2003; Kofron et al., 2002; Ruiz et al., 1996; Stepniak et al.,
2009 ). This rich milieu of pathways underscores the importance of adherens
junctional regulation in development.