MSH HOMEOBOX GENES REGULATE CADHERIN-MEDIATED CELL-ADHESION AND CELL-CELL SORTING

Msx-1 and Msx-2 are two closely related homeobox genes expressed in ce phalic neural crest tooth buds, the optic cup endocardial cushions, an d the developing limb [Hill and Davidson, 1991; Monaghan et al., 1991; Robert et al., 1991]. These sites correspond to regions of active cel l segregation and proliferation under the influence of epithelial-mese nchymal cell interactions [Brown et al., 1993; Davidson et al., 1991], suggesting that Msx-1 and Msx-2 regulate cell-cell interactions. We h ave investigated the potential relationship between expression of the Msh homeobox genes (Msx-1 and Msx-2) and cadherin-mediated cell adhesi on and cell sorting. We report that cell lines stably expressing Msx-1 or Msx-2 differentially sort on the basis of Msh gene expression. We demonstrate in vitro that initial cell aggregation involves calcium-de pendent adhesion molecules (cadherins) and that Msh genes regulate cad herin-mediated adhesion. These results support the hypothesis that Msh genes play a role in the regulation of cell-cell adhesion and provide a link between the genetic phenomena of homeobox gene expression and cellular events involved in morphogenesis, including cell sorting and proliferation. (C) 1998 Wiley-Liss, Inc.