|
|
|
|
|
|
|
||
J. Cell Biol.,
Volume 143, Number 6, December 14, 1998 1725-1734
* Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Previous studies showed that conotruncal
heart malformations can arise with the increase or decrease in Developmental Biology Program,
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912-2640; and § Department of
Cell Biology, The Scripps Research Institute, La Jolla, California 92037
1 connexin function in neural crest cells. To
elucidate the possible basis for the quantitative requirement for 1 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 1 connexins, and from 1 connexin knockout (KO) mice and FC
transgenic mice expressing a dominant-negative 1 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 1 connexin KO embryos. Migration changes occurred in step with connexin gene or transgene dosage
in the homozygous vs. hemizygous 1 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 1
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 1 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
1 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 1 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 1 connexin function.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
