ZFIN ID: ZDB-PUB-170313-1
Loss of Gspt1l disturbs the patterning of the brain central arteries in zebrafish
Wang, H., Luo, L., Yang, D.
Date: 2017
Source: Biochemical and Biophysical Research Communications   486(1): 156-162 (Journal)
Registered Authors: Luo, Lingfei
Keywords: Central artery, Gspt1l, Unfolded protein response, Vegfa, Zebrafish
MeSH Terms:
  • Activating Transcription Factor 4/genetics
  • Activating Transcription Factor 4/metabolism
  • Animals
  • Apoptosis/genetics
  • Arteries/embryology
  • Arteries/metabolism*
  • Base Sequence
  • Body Patterning/genetics*
  • Brain/blood supply*
  • Cell Cycle Proteins/genetics*
  • Cell Cycle Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • In Situ Hybridization, Fluorescence
  • Mutation*
  • Neovascularization, Physiologic/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhombencephalon/blood supply
  • Unfolded Protein Response/genetics
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 28285134 Full text @ Biochem. Biophys. Res. Commun.
The cranial vasculature is crucial for the survival and development of the central nervous system and is closely related to brain pathologies. Characterizations of the underlying mechanisms by which cranial vessels acquire their stereotypic patterning remain to be the key interest in the cerebrovascular research. In this report, we show an interesting zebrafish cq37 mutant displaying aberrant patterning of the central arteries. Genetic mapping results indicate that the gene responsible for cq37 encodes G1 to S phase transition 1, like (Gspt1l) with a nonsense mutation. Complementation studies with a CRISPR-generated allele, as well as mRNA rescues, together strongly demonstrate that gspt1l is the cq37 gene. Zebrafish gspt1l is broadly expressed in the brain with enhanced expression in hindbrain during central artery sprouting. Further studies reveal that vascular endothelial growth factor (VEGF) signaling and unfolded protein response (UPR) pathway are activated in gspt1lcq37 mutants. In addition, expression analysis shows that vegfa and activating transcription factor-4 (atf4) are strongly upregulated in regions of gspt1l expression. Our results suggest that loss of Gspt1l activates the UPR pathway, which in turn induces ectopic expression of vegfa via Atf4, thus disturbing the patterning of the central arteries.