Developing somites express two subtypes of classic cadherin adhesion recept
ors, N-cadherin and cadherin-11 (cad11). To investigate the role of these a
dhesion molecules in somite morphogenesis, we analyzed the somites of mice
whose N-cadherin and cad11 genes were disrupted. The epithelial somites of
N-cadherin null mutant mice were fragmented as reported, whereas those of c
ad11(-/-) mice showed no structural anomaly. In mice double homozygous for
N-cadherin and cad11 mutation, however, somites were further fragmented int
o smaller clusters than in the N-cadherin-deficient mice, suggesting that t
hese two cadherins cooperate in the maintenance of epithelial somites. Desp
ite the disorganization of epithelial structures, dorsoventral polarity mar
kers were expressed in their correct patterns in all of these mutant somite
s. Uncx4.1, whose expression is localized only in the caudal region of each
somite, was also expressed in a normal pattern in the mutant somites. Howe
ver, the staining for Uncx4.1 revealed that, in the N-cadherin mutants, eac
h somite tended to be cleaved at the border between the Uncx4.1-positive an
d -negative regions and that the cleaved subunits maintained the clustered
state, often exhibiting epithelioid morphology. This separation of the rost
ral and caudal regions was observed as soon as the epithelial somites had b
een formed. In the N-cadherin/cad11 double homozygous mutants, this tendenc
y was also observed, although each half of the somite further disintegrated
into randomly arranged cell clusters. These results suggest that cells of
the rostral and caudal regions of each epithelial somite have an activity t
o aggregate independently or separate from one another and that one role of
N-cadherin and cad11 is to connect the two halves into a single unit. (C)
1999 Academic Press.