Differential adhesion leads to segregation and exclusion of N-cadherin-deficient cells in chimeric embryos.
Cadherin-mediated cell-cell interactions are thought to be critical in controlling cell sorting during embryogenesis. Here, we report that chimeric embryos generated with N-cadherin-deficient (N-cadherin(-/-)) embryonic stem cells develop further than embryos completely lacking N-cadherin only when the myocardium consists of N-cadherin-positive cells. Initially, the N-cadherin-negative and -positive cells mix together to form chimeric tissues; however, by embryonic day 9.5, the N-cadherin(-/-) cells segregate from the wild-type cells forming distinct aggregates. The chimeric embryos have large aggregates of N-cadherin(-/-) myocardial cells in the heart lumen, indicating that the cells are unable to maintain cell-cell contacts with N-cadherin-positive myocytes. This sorting-out phenomenon also is apparent in somites, neural tube, and developing brain where N-cadherin(-/-) cells form distinct lumenal structures. These studies demonstrate that N-cadherin-mediated adhesion is critical for maintaining cell-cell interactions in tissues undergoing active cellular rearrangements and increased mechanical stress associated with morphogenesis.
Kostetskii
I
I
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Moore
R
R
Kemler
R
R
Radice
G L
GL
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002678:Chimera; D005314:Embryonic and Fetal Development; D006321:Heart / Q000196:embryology; D051379:Mice; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology; D013234:Stem Cells
D015820:Cadherins