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Related Experiment Videos

A role for Timeless in epithelial morphogenesis during kidney development.

Z Li1, R O Stuart, J Qiao

  • 1Departments of Pediatrics and Medicine, Division of Nephrology and Hypertension, University of California at San Diego, La Jolla, CA 92093-0693, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 30, 2000
PubMed
Summary
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The mammalian Timeless (mTim) gene is crucial for kidney development. Down-regulating mTim significantly inhibits ureteric bud branching morphogenesis and embryonic kidney growth.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Branching morphogenesis is essential for epithelial organ development, particularly in the kidney.
  • Ureteric bud (UB) cells undergo branching morphogenesis influenced by metanephric mesenchyme factors.

Purpose of the Study:

  • To identify early transcription factors involved in ureteric bud branching morphogenesis.
  • To investigate the role of the mammalian ortholog of Timeless (mTim) in kidney development.

Main Methods:

  • Targeted genetic screening to identify immediate early genes (IEGs).
  • Analysis of mTim expression patterns in embryonic organs.
  • Gene down-regulation studies in organ culture using isolated ureteric buds and embryonic kidneys.

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Main Results:

  • mTim was identified as a potential IEG involved in UB branching.
  • mTim exhibits expression patterns consistent with a role in epithelial organogenesis, notably in the developing kidney.
  • Selective mTim down-regulation profoundly inhibited embryonic kidney growth and UB morphogenesis.
  • mTim down-regulation in isolated UBs inhibited morphogenesis, indicating a direct role in the epithelial cell pathway.

Conclusions:

  • mTim plays a critical role in embryonic kidney growth and ureteric bud branching morphogenesis.
  • mTim is a key regulator in the epithelial cell morphogenetic pathway essential for forming branching tubules.