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.

 
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