ZFIN ID: ZDB-PUB-150722-7
von Hippel-Lindau gene plays a role during zebrafish pronephros development
Chen, Y.H., Chang, C.F., Lai, Y.Y., Sun, C.Y., Ding, Y.J., Tsai, J.N.
Date: 2015
Source: In vitro cellular & developmental biology. Animal   51(10): 1023-32 (Journal)
Registered Authors: Chen, Yau-Hung, Ding, Yu-Ju
Keywords: vhl, Zebrafish, Pronephros development, Renal function, Vegfa
MeSH Terms:
  • Animals
  • Dextrans/metabolism
  • Gene Knockdown Techniques
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
  • Kidney Glomerulus/embryology*
  • Models, Animal
  • Morpholinos/genetics
  • Neovascularization, Physiologic/genetics
  • Organogenesis/genetics*
  • Podocytes/metabolism
  • Polycythemia/genetics
  • Pronephros/abnormalities
  • Pronephros/embryology*
  • RNA, Messenger/genetics
  • Signal Transduction/genetics
  • Ubiquitination
  • Vascular Endothelial Growth Factor A/metabolism*
  • Von Hippel-Lindau Tumor Suppressor Protein/genetics*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism*
  • Zonula Occludens-1 Protein/metabolism
PubMed: 26194803 Full text @ In Vitro Cell Dev. Biol. Anim.
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ABSTRACT
von Hippel-Lindau (pVHL)-mediated ubiquitination of HIF-1α plays a central role in the cellular responses to changes in oxygen availability. In the present study, using zebrafish as a model, we showed that specific knockdown of endogenous vhl leads to pronephros malformation and renal failure. Knockdown of vhl resulted in abnormal kidney development, including curved and cystic pronephric tubule or/and cystic and atrophic glomerulus. Co-injecting capped vhl messenger RNA (mRNA) partially rescued pronephros morphant phenotype, confirming the specificity of the morpholino oligonucleotide (MO)-induced pronephric defects. In keeping with the pronephros phenotype, renal function was affected as well in vhl morphants. Dextran clearance abilities of vhl morphants were significantly reduced as compared with those of control embryos. Further analysis indicated that glomerular integrity is impaired in vhl morphants, while the organization of pronephric duct was minimally affected. Vhl morphants display global increased vegf signaling and angiogenesis. In addition, we found that vhl morphants displayed elevated expression of vegfa in podocytes and increased angiogenesis at pronephric glomerulus and the nearby vessels. Treatment of vegf inducer to embryos also caused pronephros phenotype resembling vhl morphants, further supporting that increased vegfa signaling contribute to the pronephros morphant phenotype. Our study establishes the zebrafish as an alternative vertebrate model system for studying Vhl function during kidney development.
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