Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube.

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  • Author(s): Liu S;Liu S; Liu F; Schneider AE; St Amand T; Epstein JA; Gutstein DE
  • Source:
    Development (Cambridge, England) [Development] 2006 May; Vol. 133 (10), pp. 2063-73. Date of Electronic Publication: 2006 Apr 19.
  • Publication Type:
    Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • 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:
      Connexin 43/*deficiency ; Heart/*embryology ; Heart Defects, Congenital/*genetics ; Neural Crest/*pathology; Animals ; Animals, Newborn ; Connexin 43/genetics ; Heart Defects, Congenital/embryology ; Heart Ventricles/abnormalities ; Mice ; Mice, Transgenic ; Myocardium/pathology
    • Abstract:
      Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior studies suggest a vital role for CNC expression of Cx43 in heart development. Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT phenotype, although coronary vasculature was abnormal in this mutant line. A broader CKO mediated by P3pro (Pax3)-Cre, involving both ventral and dorsal aspects of the thoracic neural tube and CNC, resulted in infundibular bulging and coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre-mediated loss of Cx43 in the neural tube was characterized by a late phase of cellular delamination from the dorsal and lateral neural tube, a markedly increased abundance of neuroepithelium-derived cells outside of the neural tube and an excess of such cells infiltrating the heart and infundibulum. Thus, expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43 is not required in the CNC for normal OFT morphogenesis. Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development.
    • Grant Information:
      R01 HL081336 United States HL NHLBI NIH HHS; HL61475 United States HL NHLBI NIH HHS; HL081336 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Connexin 43)
    • Publication Date:
      Date Created: 20060421 Date Completed: 20060713 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      10.1242/dev.02374
    • Accession Number:
      16624854