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Related Experiment Videos

Inositol polyphosphates regulate zebrafish left-right asymmetry.

Bhaskarjyoti Sarmah1, Andrew J Latimer, Bruce Appel

  • 1Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21(st) Avenue South, Nashville, Tennessee 37232, USA.

Developmental Cell
|July 5, 2005
PubMed
Summary

Inositol hexakisphosphate production is crucial for establishing left-right body asymmetry in zebrafish. Disrupting inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1) function leads to randomized organ placement and gene expression due to altered calcium signaling.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Vertebrate body plans exhibit conserved left-right (LR) asymmetry in organ positioning.
  • Cilia-driven fluid flow across the node is hypothesized to establish LR asymmetry via asymmetric calcium (Ca2+) signaling.

Purpose of the Study:

  • To investigate the role of inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1) in zebrafish LR axis determination.
  • To elucidate the molecular mechanisms linking Ipk1 to asymmetric Ca2+ signaling.

Main Methods:

  • Zebrafish embryo manipulation using antisense morpholino oligonucleotides to knockdown ipk1 expression.
  • Analysis of LR-specific gene expression and organ placement.
  • Measurement of intracellular Ca2+ flux in ciliated cells.

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Main Results:

  • Zebrafish embryos express ipk1 symmetrically during early development.
  • ipk1 knockdown randomized LR-specific gene expression and organ positioning.
  • Reduced intracellular Ca2+ flux was observed in cells surrounding the Kupffer's vesicle in ipk1 knockdown embryos.

Conclusions:

  • Inositol hexakisphosphate production pathway, regulated by Ipk1, is essential for normal LR axis determination in zebrafish.
  • Ipk1 plays a critical role in regulating asymmetric Ca2+ flux during LR specification.
  • These findings highlight a novel molecular player in the fundamental process of establishing body asymmetry.