I. Kostetskii et al., Differential adhesion leads to segregation and exclusion of N-cadherin-deficient cells in chimeric embryos, DEVELOP BIO, 234(1), 2001, pp. 72-79
Cadherin-mediated cell-cell interactions are thought to be critical in cont
rolling cell sorting during embryogenesis. Here, we report that chimeric em
bryos 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-cadh
erin-negative and -positive cells mix together to form chimeric tissues; ho
wever, by embryonic day 9.5, the N-cadherin(-/-) cells segregate from the w
ild-type cells forming distinct aggregates. The chimeric embryos have large
aggregates of N-cadherin(-/-) myocardial cells in the heart lumen, indicat
ing that the cells are unable to maintain cell-cell contacts with N-cadheri
n-positive myocytes. This sorting-out phenomenon also is apparent in somite
s, neural tube, and developing brain where N-cadherin(-/-) cells form disti
nct lumenal structures. These studies demonstrate that N-cadherin-mediated
adhesion is critical for maintaining cell-cell interactions in tissues unde
rgoing active cellular rearrangements and increased mechanical stress assoc
iated with morphogenesis. (C) 2001 Academic Press.