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Related Experiment Videos

Timeless in lung morphogenesis.

Jing Xiao1, Changgong Li, Nian-Ling Zhu

  • 1School of Medicine, University of Southern California, Los Angeles, California 90033, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|September 2, 2003
PubMed
Summary

Mouse TIMELESS (mTIM) is crucial for embryonic lung development, regulating branching morphogenesis. Its conserved function highlights its importance in organ formation requiring similar developmental processes.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • The Clock gene, timeless, regulates circadian rhythm in Drosophila.
  • Its vertebrate homolog, TIMELESS (TIM), is critical for embryonic development, particularly in murine urethral bud branching morphogenesis.

Purpose of the Study:

  • To investigate the distribution and role of mouse TIMELESS (mTIM) during lung development, a process involving branching morphogenesis.
  • To understand the conserved function of Timeless in organ formation.

Main Methods:

  • Generated a polyclonal antibody to mouse TIMELESS (mTIM).
  • Studied mTIM distribution in mouse embryos using immunostaining at various developmental stages (E9.5, E15).
  • Utilized antisense oligonucleotides to inhibit mTim in explant cultures of embryonic lungs.

Related Experiment Videos

  • Examined mTIM expression in isolated alveolar type 2 cells and cultured lung cells.

    • Main Results:

    • TIM was localized to all early embryonic organs, notably the neural epithelium.
    • During lung morphogenesis, TIM was present in both epithelial and mesenchymal cells, decreasing in mesenchyme by E15 but remaining pronounced in airway epithelium.
    • TIM localized to alveolar type 2 cells and CCSP-positive nonciliated columnar epithelial cells in proximal airways.
    • Antisense oligonucleotides targeting mTim specifically inhibited embryonic lung branching morphogenesis without affecting SpC expression.
    • TIM expression in cultured lung cells was independent of cell cycle and proliferation.

    Conclusions:

    • Mouse TIMELESS (mTIM) plays a critical role in embryonic lung branching morphogenesis.
    • The function of Timeless appears to be conserved in organs that require branching morphogenesis for their formation.