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Related Experiment Videos

Left-right development: mammalian phenotypes and conceptual models

A Lander1, T King, N A Brown

  • 1Birmingham Children's Hospital, Ladywood Middleway, UK.

Seminars in Cell & Developmental Biology
|May 8, 1998
PubMed
Summary
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A new two-gradient model explains consistent left-right body asymmetry and associated developmental defects. This model accounts for various situs abnormalities, including isomerism and heterotaxia, by proposing a molecular chiral referent.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Consistent left-right asymmetry is crucial for normal development and requires specific developmental pathways.
  • Existing models struggle to explain the complex phenotypes observed in left-right asymmetry defects, such as randomization of situs, isomerism, and heterotaxia.
  • Current hypotheses suggest a molecular chiral referent initiates the primary handed information for asymmetry.

Purpose of the Study:

  • To propose a novel model that explains the development of consistent left-right asymmetry.
  • To account for a wide range of situs defects, including isomerism and heterotaxia, within a unified framework.
  • To refine understanding of the molecular mechanisms underlying body asymmetry.

Main Methods:

  • Development of a new theoretical two-gradient model.

Related Experiment Videos

  • Analysis of existing data on human and mouse mutations affecting left-right asymmetry.
  • Computational modeling to assess the model's ability to predict observed phenotypes.

    • Main Results:

    • The proposed two-gradient model successfully accommodates various defects in situs, including randomization, isomerism, and heterotaxia.
    • The model maintains the integrity of the primary asymmetry while explaining secondary defects.
    • It provides a framework for understanding how disruptions in developmental pathways lead to complex asymmetry phenotypes.

    Conclusions:

    • The two-gradient model offers a comprehensive explanation for the diverse outcomes of disrupted left-right asymmetry.
    • This model advances our understanding of developmental processes governing body handedness.
    • It highlights the importance of gradient-based mechanisms in establishing and perturbing biological asymmetry.