Connexin43 levels are increased in mouse neural crest cells exposed to homocysteine.
BACKGROUND
Elevated homocysteine levels during embryonic development can result in neural tube and cardiovascular defects. The mechanisms that underlie the toxic effect of homocysteine are largely unknown.


METHODS
We cultured mouse neural tube explants to study the effects of homocysteine on the migratory behavior of neural crest cells and on the levels of the gap junction protein Connexin43 (Cx43) and the actin- and Cx43-interacting protein ZO-1.


RESULTS
Homocysteine exposure resulted in a significantly augmented maximal migration distance (MMD). The level of Cx43 immunolabeling was 2 times higher in the cytoplasm and cell protrusions of neural crest cells in homocysteine-treated cultures than in control cultures. Furthermore, colocalization of Cx43 and ZO-1 was increased in neural crest cell protrusions by this treatment.


CONCLUSIONS
Increased Cx43 levels were previously shown to result in abnormal embryonic development. Our data raises the hypothesis that the embryotoxic effects of homocysteine may be mediated in part by its effects on Cx43 expression level and gap junction function in neural crest cells.
Boot
Marit J
MJ
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. m.j.boot@hgu.mrc.ac.uk
Gittenberger-de Groot
Adriana C
AC
Poelmann
Robert E
RE
Gourdie
Robert G
RG
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D018031:Connexin 43 / Q000096:biosynthesis / Q000378:metabolism*; D006710:Homocysteine / Q000502:physiology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D062826:Zonula Occludens-1 Protein
D018031:Connexin 43; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D006710:Homocysteine