Hdl Handle:
http://hdl.handle.net/10675.2/545
Title:
Gap Junctionâ mediated Cellâ Cell Communication Modulates Mouse Neural Crest Migration
Authors:
Huang, G.Y.; Cooper, E.S.; Waldo, K.; Kirby, M.L.; Gilula, N.B.; Lo, C.W.
Abstract:
Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in a1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for a1 connexin 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 a1 connexins, and from a1 connexin knockout (KO) mice and FC transgenic mice expressing a dominant-negative a1 connexin fusion protein. These studies showed that the migration rate of cardiac neural crest was increased in the CMV43 embryos, but decreased in the FC transgenic and a1 connexin KO embryos. Migration changes occurred in step with connexin gene or transgene dosage in the homozygous vs. hemizygous a1 connexin KO 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 and a1 connexin KO 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 the a1 connexin KO 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 the a1 connexin KO 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 a1 connexins 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 a1 connexin function.
Citation:
J Cell Biol. 1998 Dec 14; 143(6):1725-1734
Issue Date:
14-Dec-1998
URI:
http://hdl.handle.net/10675.2/545
PubMed ID:
9852163
PubMed Central ID:
PMC2132985
Type:
Article
ISSN:
1540-8140
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorHuang, G.Y.en_US
dc.contributor.authorCooper, E.S.en_US
dc.contributor.authorWaldo, K.en_US
dc.contributor.authorKirby, M.L.en_US
dc.contributor.authorGilula, N.B.en_US
dc.contributor.authorLo, C.W.en_US
dc.date.accessioned2012-10-26T16:26:36Z-
dc.date.available2012-10-26T16:26:36Z-
dc.date.issued1998-12-14en_US
dc.identifier.citationJ Cell Biol. 1998 Dec 14; 143(6):1725-1734en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid9852163en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/545-
dc.description.abstractPrevious studies showed that conotruncal heart malformations can arise with the increase or decrease in a1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for a1 connexin 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 a1 connexins, and from a1 connexin knockout (KO) mice and FC transgenic mice expressing a dominant-negative a1 connexin fusion protein. These studies showed that the migration rate of cardiac neural crest was increased in the CMV43 embryos, but decreased in the FC transgenic and a1 connexin KO embryos. Migration changes occurred in step with connexin gene or transgene dosage in the homozygous vs. hemizygous a1 connexin KO 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 and a1 connexin KO 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 the a1 connexin KO 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 the a1 connexin KO 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 a1 connexins 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 a1 connexin function.en_US
dc.titleGap Junctionâ mediated Cellâ Cell Communication Modulates Mouse Neural Crest Migrationen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2132985en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.