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Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature

I A Graef1, F Chen, L Chen

  • 1Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

Cell
|July 6, 2001
PubMed

Insights

Early calcineurin/NFAT signaling is crucial for vascular development. Disrupting these pathways causes severe vessel defects, highlighting their role in tissue communication during embryogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Vascular development depends on intercellular signaling, but intracellular pathways remain unclear.
  • Nuclear Factor of Activated T-cells (NFAT) proteins are key regulators of cellular responses.
  • Calcineurin is a phosphatase that regulates NFAT nuclear localization.

Purpose of the Study:

  • To investigate the role of calcineurin/NFAT signaling in embryonic vascular development.
  • To determine the specific timing and necessity of calcineurin function in this process.

Main Methods:

  • Generation and analysis of mice with disrupted NFATc3/NFATc4 genes.
  • Creation and study of mice with a mutation in the calcineurin B gene affecting phosphatase activity.
  • Examination of vascular morphology and development at embryonic stages.

Main Results:

  • Mice lacking NFATc3 and NFATc4 exhibited severe vascular assembly defects and abnormal vessel growth.
  • Mice with a calcineurin B mutation showed similar vascular abnormalities, indicating calcineurin's essential role.
  • Calcineurin function was specifically required during a narrow window between embryonic days 7.5 and 8.5.

Conclusions:

  • Early calcineurin/NFAT signaling is indispensable for proper vascular patterning.
  • This signaling pathway initiates critical crosstalk between vessels and surrounding tissues.
  • Defects in this early signaling lead to widespread vascular developmental failures.

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