Outstanding Questions:
(i)
intercellular mechanisms that allow cell-cell communication,
(ii)
signaling pathways that lead to regulation of contact inhibition of cell migration, and proliferation,
(iii)
molecular events that lead to targeting and recruitment of the tight junction scaffold,
(iv)
mechanisms that lead to assembly of tight junction membrane micro-domain, paracellular channels, and intramembraneous strands,
(v) extracellular adhesive interactions and their regulation,
(vi)
intracellular cytoskeletal interactions and their regulation,
(vii)
contribution to morphogenesis and tensile strength of the epithelial sheet,
(viii)
maintenance of a steady-state through regulation of protein synthesis and membrane recycling, and
(ix)
generation of polarity during differentiation and epithelialization.
The current knowledge
of known tight junction proteins is far from explaining even one of these complex processes.
