Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis

Afadin is an actin filament-binding protein that binds to nectin. an immuno globulin-like cell adhesion molecule, and is colocalized with nectin at cad herin-based cell-cell adherens junctions (AJs),To explore the function of a fadin in cell-cell adhesion during embryogenesis, we generated afadin(-/-) mice and embryonic stem cells. In wild-type mice at embryonic days 6.5-8.5, afadin was highly expressed in the embryonic ectoderm and the mesoderm, bu t hardly detected in the extraembryonic regions such as the visceral endode rm. Afadin; mice showed developmental defects at stages during and after ga strulation, including disorganization of the ectoderm, impaired migration o f the mesoderm, and loss of somites and other structures derived from both the ectoderm and the mesoderm. Cystic embryoid bodies derived from afadin(- /-) embryonic stem cells showed normal organization of the endoderm but dis organization of the ectoderm. Cell-cell AJs and tight junctions were improp erly organized in the ectoderm of afadin(-/-) mice and embryoid bodies. The se results indicate that afadin is highly expressed in the ectoderm-derived cells during embryogenesis and plays a key role in proper organization of AJs and tight junctions of the highly expressing cells, which is essential for proper tissue morphogenesis.