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 cephalic neural crest tooth buds, the optic cup endocardial cushions, and the developing limb [Hill and Davidson, 1991; Monaghan et al., 1991; Robert et al., 1991]. These sites correspond to regions of active cell segregation and proliferation under the influence of epithelial-mesenchymal cell interactions [Brown et al., 1993; Davidson et al., 1991], suggesting that Msx-1 and Msx-2 regulate cell-cell interactions. We have investigated the potential relationship between expression of the Msh homeobox genes (Msx-1 and Msx-2) and cadherin-mediated cell adhesion 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-dependent adhesion molecules (cadherins) and that Msh genes regulate cadherin-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.
Lincecum
J M
JM
Joint Program in Neonatology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fannon
A
A
Song
K
K
Wang
Y
Y
Sassoon
D A
DA
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics*; D002460:Cell Line; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D051957:MSX1 Transcription Factor; D051379:Mice; D014157:Transcription Factors
D015820:Cadherins; D004268:DNA-Binding Proteins; C096010:Dr protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; D014157:Transcription Factors; D002118:Calcium