Desmosomes are intercellular junctions of epithelia and are of widespread i
mportance in the maintenance of tissue architecture. We provide evidence th
at desmosomal adhesion has a function in epithelial morphogenesis and cell-
type-specific positioning. Blocking peptides corresponding to the cell adhe
sion recognition (CAR) sites of desmosomal cadherins block alveolar morphog
enesis by epithelial cells from mammary lumen. Desmosomal CAR-site peptides
also disrupt positional sorting of luminal and myoepithelial cells in aggr
egates formed by the reassociation of isolated cells. We demonstrate that d
esmosomal cadherins and E-cadherin are comparably involved in epithelial mo
rphoregulation. The results indicate a wider role for desmosomal adhesion i
n morphogenesis than has previously been considered.