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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
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Intronic delay is essential for oscillatory expression in the segmentation clock.

Yoshiki Takashima1, Toshiyuki Ohtsuka, Aitor González

  • 1Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|February 9, 2011
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Introns in the Hes7 gene create a crucial delay, enabling oscillations necessary for proper somite segmentation. Removing introns disrupts this timing, causing severe developmental defects in mice.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Precise gene expression timing is vital for biological processes, yet the underlying molecular mechanisms are poorly understood.
  • Introns, non-coding DNA sequences, are hypothesized to play a role in regulating gene expression timing, but this remains largely untested in natural gene systems.
  • The somite segmentation clock, an oscillator network, relies on negative feedback with delayed timing, making it an ideal model to study intronic roles.

Purpose of the Study:

  • To investigate the role of introns in the timing of Hes7 gene expression within the somite segmentation clock.
  • To determine if intronic sequences are essential for the oscillatory expression of Hes7 and subsequent proper embryonic development.

Main Methods:

  • Utilized mathematical modeling to predict the impact of delayed gene expression on Hes7 oscillations.
  • Generated genetically modified mice lacking introns at the Hes7 locus.
  • Analyzed Hes7 gene expression patterns and somite segmentation in both wild-type and intron-deficient mice.

Main Results:

  • Introns in the Hes7 gene were found to introduce an approximate 19-minute delay in gene expression.
  • Mathematical modeling indicated that Hes7 oscillations would cease without this intronic delay.
  • Mice lacking Hes7 introns exhibited continuous, non-oscillatory Hes7 expression and severe defects in somite segmentation.

Conclusions:

  • Introns are essential for maintaining the oscillatory expression of the Hes7 gene.
  • Intronic delays are critical for the dynamic regulation of gene expression required for embryonic segmentation.
  • This study highlights the significant functional role of introns in biological timing mechanisms.