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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Inherent Dynamics Visualizer, an Interactive Application for Evaluating and Visualizing Outputs from a Gene Regulatory Network Inference Pipeline
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sizzled function and secreted factor network dynamics.

Jianli Shi1, Huarong Zhang, Robin D Dowell

  • 1Molecular, Cellular and Developmental Biology, University of Colorado , Boulder, CO 80309-0347 , USA.

Biology Open
|December 6, 2012
PubMed
Summary
This summary is machine-generated.

Sizzled, a secreted protein, is crucial for mesoderm development and neural crest induction in Xenopus embryos. Its down-regulation disrupts Wnt and BMP signaling, impacting embryonic patterning and organ formation.

Keywords:
BMPNeural crest inductionSecreted signaling antagonistsSignaling networksWNTsizzled

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Area of Science:

  • Developmental Biology
  • Molecular Embryology
  • Signal Transduction

Background:

  • Snail2 (Slug) is an E-box binding transcription factor involved in neural crest induction.
  • The secreted protein sizzled possesses both Wnt and BMP inhibitor activities.
  • Previous studies highlighted Snail2's role in mesoderm-induced neural crest formation.

Purpose of the Study:

  • To investigate the role of sizzled in Xenopus embryonic development, specifically in mesodermal patterning and neural crest induction.
  • To elucidate the signaling pathways regulated by sizzled during early Xenopus embryogenesis.
  • To understand the relationship between sizzled, Wnt, and BMP signaling in embryonic development.

Main Methods:

  • Morpholino-mediated knockdown of sizzled expression in Xenopus embryos.
  • Analysis of mesodermal and neural crest marker gene expression (e.g., brachyury).
  • Rescue experiments involving co-injection of RNAs encoding Wnt and BMP inhibitors (Noggin, SFRP2, Dickkopf).

Main Results:

  • Down-regulation of sizzled led to decreased expression of the mesodermal marker brachyury.
  • Sizzled deficiency resulted in defects in neural crest induction, pronephros formation, and muscle patterning.
  • Loss of sizzled reduced levels of secreted Wnt inhibitor SFRP2 and BMP inhibitor Noggin RNA.
  • Sizzled morphant phenotypes were rescued by co-expressing Noggin with SFRP2 or Dickkopf.

Conclusions:

  • Sizzled plays a critical role in mesodermal patterning and neural crest induction in Xenopus.
  • Sizzled functions within a dynamic BMP and Wnt signaling network.
  • These findings expand the known functions of sizzled beyond dorsal-ventral patterning.