Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Xu X;Xu X; Francis R; Wei CJ; Linask KL; Lo CW
  • Source:
    Development (Cambridge, England) [Development] 2006 Sep; Vol. 133 (18), pp. 3629-39. Date of Electronic Publication: 2006 Aug 16.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Intramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Company Of Biologists Limited Country of Publication: England NLM ID: 8701744 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0950-1991 (Print) Linking ISSN: 09501991 NLM ISO Abbreviation: Development Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge Eng : Company Of Biologists Limited
      Original Publication: [Cambridge] : Company of Biologists, [c1987-
    • Subject Terms:
      Cell Movement/*physiology ; Connexin 43/*genetics ; Neural Crest/*cytology; Actins/metabolism ; Animals ; Blotting, Western ; Cell Adhesion/genetics ; Cell Adhesion/physiology ; Cell Movement/genetics ; Cell Polarity/genetics ; Cell Polarity/physiology ; Cells, Cultured ; Connexin 43/metabolism ; Connexin 43/physiology ; Cytoskeleton/metabolism ; Fibronectins/metabolism ; Gap Junctions/metabolism ; Immunohistochemistry ; Immunoprecipitation ; Integrin beta1/metabolism ; Mice ; Mice, Knockout ; Neural Crest/metabolism ; Neural Crest/physiology ; Protein Binding ; Vinculin/metabolism
    • Abstract:
      Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.
    • Grant Information:
      United States Intramural NIH HHS
    • Accession Number:
      0 (Actins)
      0 (Connexin 43)
      0 (Fibronectins)
      0 (Integrin beta1)
      125361-02-6 (Vinculin)
    • Publication Date:
      Date Created: 20060818 Date Completed: 20070104 Latest Revision: 20171116
    • Publication Date:
      20240829
    • Accession Number:
      10.1242/dev.02543
    • Accession Number:
      16914489