THE
ROLE OF N-CADHERIN IN THE MODULATION OF MOUSE NEURAL CREST CELL MIGRATION
Huang GY1, Xu X2, Radice GLR2 and Lo CW2
1Children��s Hospital of Fudan University, Shanghai,
China
2University of Pennsylvania, Philadelphia, PA
Objective: To observe the role of N-cadherin in regulating gap junction
communication and the migration of cardiac neural crest cells, which is
important in morphogenesis of conotruncal outflow tract of the heart.
Methods:
The N-cadherin knockout mouse was used in the study. The approaches
included a neural crest outgrowth culture system, dye coupling analysis,
immunohistochemical analysis and time lapse video microscopy.
Results:
Dye coupling analysis showed that gap junction communication was greatly
reduced in the N-cadherin deficient neural crest cells, to levels similar
to that of the Cx43 knockout mouse. Measurements of neural crest outgrowth
area in neural tube explant cultures revealed a reduction in the apparent
rate of crest cell migration. Time lapse video microscopy showed no change
in the time of crest cell emergence. Unexpectedly, motion analysis revealed
that the speed of neural crest cell locomotion was elevated, but this was
accompanied by a reduction in the directionality of cell movement. Immunohistochemical analysis of
wildtype mouse embryos confirmed that N-cadherin is expressed in migrating
neural crest cells. In N-cadherin deficient embryos, expression of b-catenin and Cx43 gap junctions were markedly
reduced.
Conclusion:
N-cadherin plays an important
role in cardiac neural crest cell migration, and this likely involves the
modulation of gap junction communication mediated by Cx43.