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Related Experiment Videos

Gap junction-mediated cell-cell communication modulates mouse neural crest migration

G Y Huang1, E S Cooper, K Waldo

  • 1Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

The Journal of Cell Biology
|December 16, 1998
PubMed
Summary
This summary is machine-generated.

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Altered alpha1 connexin levels impact cardiac neural crest cell migration and heart development. Both increased and decreased connexin function disrupt normal heart formation by affecting neural crest cell movement.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Conotruncal heart malformations are linked to altered alpha1 connexin function in neural crest cells.
  • Understanding the quantitative role of alpha1 connexin gap junctions is crucial for cardiac development.

Purpose of the Study:

  • To investigate the quantitative requirement for alpha1 connexin gap junctions in cardiac neural crest cell migration.
  • To elucidate the basis for conotruncal heart defects associated with alpha1 connexin dysfunction.

Main Methods:

  • Utilized a neural crest outgrowth culture system with transgenic mice overexpressing or lacking alpha1 connexins.
  • Assessed neural crest cell migration rates, dye coupling for gap junction communication, and in vivo distribution using lacZ transgenes.

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  • Examined cell proliferation in myocardium in response to altered neural crest cell behavior.

    • Main Results:

    • Increased alpha1 connexin expression enhanced cardiac neural crest migration; knockout and dominant-negative mutants showed decreased migration.
    • Gap junction communication levels directly correlated with alpha1 connexin dosage.
    • Reduced gap junction communication, via genetic manipulation or oleamide, impaired neural crest migration.
    • In vivo studies revealed altered neural crest cell distribution and myocardial proliferation in transgenic/KO mice.
    • Cardiac neural crest cells appear to influence myocardial growth and development.

    Conclusions:

    • Alpha1 connexin-mediated gap junction communication is essential for normal cardiac neural crest migration.
    • Perturbations in cardiac neural crest migration due to alpha1 connexin dysfunction are a likely cause of heart defects.
    • Cardiac neural crest cells may play a regulatory role in the development of non-neural crest tissues.