Model of the effect of Sun2 loss on intercellular adhesion and cytoskeletal organization in vitro and in vivo. (A) Diagram depicting the organization of cytoskeletal elements, forces on nuclei (F in arrows), and desmosome distribution in differentiated WT and Sun2^−/− MKCs. In WT cells, the MT and actin cytoskeletons appear to impose opposing forces on the nucleus, resulting in a bias in nuclear position toward interior adhesions. Sun2^−/− cells display defective MT and actin organization; alterations in MT dynamics in Sun2^−/− cells most likely produce the observed defect in nuclear positioning. An even distribution of desmosomes along interior and lateral intercellular adhesions is disrupted in Sun2^−/− cells. (B) Sun2^−/− hair follicles exhibit a desmosome deficiency along lateral-like He–He junctions, along with alterations in desmosome morphology and intermembrane spacing, as well as an increase in desmosomes along interior-like He–Hu junctions compared with WT follicles. These changes in desmosome density parallel the changes in desmosome distribution observed in vitro.