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Related Experiment Video

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In Vitro Investigation of the Effects of the Hyaluronan-Rich Extracellular Matrix on Neural Crest Cell Migration
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Tmem2 Regulates Embryonic Vegf Signaling by Controlling Hyaluronic Acid Turnover.

Jessica E De Angelis1, Anne K Lagendijk1, Huijun Chen1

  • 1Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.

Developmental Cell
|January 25, 2017
PubMed
Summary

Zebrafish tmem2 mutants show defective angiogenesis due to increased hyaluronic acid (HA). Degrading HA or overexpressing Vegfc rescued blood vessel formation, revealing Tmem2

Keywords:
VEGFangiogenesisextracellular matrixhyaluronic acidtmem2zebrafish

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Angiogenesis is crucial for tissue vascularization in development and disease.
  • Vascular Endothelial Growth Factors (VEGFs) and their receptors orchestrate angiogenesis.
  • The role of the extracellular matrix (ECM) in regulating VEGF signaling is not fully understood.

Purpose of the Study:

  • To investigate the genetic basis of angiogenesis defects.
  • To elucidate the function of Tmem2 in developmental angiogenesis.
  • To understand the role of extracellular matrix components, specifically hyaluronic acid (HA), in regulating VEGF signaling.

Main Methods:

  • Forward genetic screen in zebrafish to identify mutants with angiogenesis defects.
  • Analysis of tmem2 zebrafish mutants exhibiting impaired arterial and venous Vegf/Vegfr/Erk signaling.
  • Assessment of angiogenesis rescue by degrading or altering hyaluronic acid (HA) levels, and by overexpressing Vegfc.

Main Results:

  • tmem2 mutants displayed significant angiogenesis defects and increased hyaluronic acid (HA) surrounding developing vessels.
  • Degradation of excess HA or overexpression of Vegfc rescued angiogenesis in tmem2 mutants.
  • These findings indicate that Tmem2 is essential for regulating HA turnover and promoting normal VEGF signaling.

Conclusions:

  • Tmem2 plays a critical role in regulating hyaluronic acid (HA) turnover during developmental angiogenesis.
  • Proper HA turnover by Tmem2 is necessary for effective VEGF signaling and blood vessel formation.
  • This study highlights a novel mechanism by which the extracellular matrix influences angiogenesis.