Gap Junction–mediated Cell–Cell Communication Modulates Mouse Neural Crest Migration

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作者：

G. Y. Huang，E. S. Cooper，K. Waldo，M. L. Kirby，N. B. Gilula and C. W. Lo

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摘要：

Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in α1connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for α1connexin gap junctions in cardiac development, a neural crest outgrowth culture system was used to examine migration of neural crest cells derived from CMV43 transgenic embryos overexpressing α1connexins, and fromα1connexinknockout (KO) mice and FC transgenic mice expressing a dominant-negativeα1connexinfusion protein. These studies showed that the migration rate of cardiac neural crest was increased in the CMV43 embryos, but decreased in the FC transgenic andα1connexinKO embryos. Migration changes occurred in step with connexin gene or transgene dosage in the homozygous vs. hemizygousα1connexinKO and CMV43 embryos, respectively. Dye coupling analysis in neural crest cells in the outgrowth cultures and also in the living embryos showed an elevation of gap junction communication in the CMV43 transgenic mice, while a reduction was observed in the FC transgenic andα1connexinKO mice. Further analysis using oleamide to downregulate gap junction communication in nontransgenic outgrowth cultures showed that this independent method of reducing gap junction communication in cardiac crest cells also resulted in a reduction in the rate of crest migration. To determine the possible relevance of these findings to neural crest migration in vivo, a lacZ transgene was used to visualize the distribution of cardiac neural crest cells in the outflow tract. These studies showed more lacZ-positive cells in the outflow septum in the CMV43 transgenic mice, while a reduction was observed in theα1connexinKO mice. Surprisingly, this was accompanied by cell proliferation changes, not in the cardiac neural crest cells, but in the myocardium— an elevation in the CMV43 mice vs. a reduction in theα1connexinKO mice. The latter observation suggests that cardiac neural crest cells may have a role in modulating growth and development of non–neural crest– derived tissues. Overall, these findings suggest that gap junction communication mediated by α1connexins plays an important role in cardiac neural crest migration. Furthermore, they indicate that cardiac neural crest perturbation is the likely underlying cause for heart defects in mice with the gain or loss of α1connexin function.

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关键词：

neural crest gap junction connexin 43 oleamide cardiac

DOI：

10.1083/jcb.143.6.1725

被引量：

276

年份：

1998