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Retinoids and mammalian development.

G M Morriss-Kay1, S J Ward

  • 1Department of Human Anatomy and Genetics, University of Oxford, United Kingdom.

International Review of Cytology
|April 20, 1999
PubMed
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Vertebrate embryos need retinoic acid (RA) for development. While some retinoid receptors show plasticity, RXR alpha is crucial for heart and eye development, and RA excess affects development differently than normal RA signaling.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Vertebrate embryonic development is critically dependent on retinoic acid (RA).
  • Mammalian systems maintain stable embryonic retinoid levels through maternal homeostasis.
  • Retinol transport to embryos involves retinol-binding protein (RBP) and cell surface receptors, with CRBP I and RA synthesis enzymes in sensitive tissues.

Purpose of the Study:

  • To investigate the role of retinoid receptors in embryonic development.
  • To understand the differential effects of physiological RA signaling versus RA excess.
  • To identify specific retinoid receptors essential for organogenesis.

Main Methods:

  • Analysis of genetic studies involving mutations in retinoid receptors (RAR/RXR).

Related Experiment Videos

  • Examination of embryogenesis in mice lacking specific RAR or RXR genes.
  • Comparison of susceptibility to RA excess in wild-type versus mutant mice.

    • Main Results:

    • Disruption of most RAR or RXR genes has minimal impact on embryogenesis, indicating functional plasticity.
    • RXR alpha is essential for normal heart and eye development.
    • Mice lacking RAR gamma or RXR alpha exhibit altered susceptibility to RA excess, suggesting distinct receptor involvement in teratogenesis versus normal development.

    Conclusions:

    • While RA signaling pathways display plasticity, specific receptors like RXR alpha are indispensable for critical developmental processes.
    • The receptors mediating teratogenic effects of RA excess may differ from those involved in physiological RA signaling.
    • Understanding these receptor specificities is key to comprehending RA's dual role in development and teratogenesis.