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 immunoglobulin-like cell adhesion molecule, and is colocalized with nectin at cadherin-based cell–cell adherens junctions (AJs). To explore the function of afadin 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, but hardly detected in the extraembryonic regions such as the visceral endoderm. Afadin^−/− mice showed developmental defects at stages during and after gastrulation, including disorganization of the ectoderm, impaired migration of 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 disorganization of the ectoderm. Cell–cell AJs and tight junctions were improperly organized in the ectoderm of afadin^−/− mice and embryoid bodies. These 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.