Role of Chd7 in Zebrafish: A Model for CHARGE Syndrome

Patten, S.A., Jacobs-McDaniels, N.L., Zaouter, C., Drapeau, P., Albertson, R.C., and Moldovan, F.
PLoS One   7(2): e31650 (Journal)
Registered Authors
Albertson, R. Craig, Drapeau, Pierre
MeSH Terms
  • Animals
  • Axons/drug effects
  • Body Patterning/drug effects
  • Body Patterning/genetics
  • CHARGE Syndrome/genetics
  • CHARGE Syndrome/metabolism*
  • Calcification, Physiologic/drug effects
  • Cell Polarity/drug effects
  • DNA Helicases/genetics
  • DNA Helicases/metabolism*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Disease Models, Animal
  • Embryonic Development/drug effects
  • Embryonic Development/genetics
  • Face/innervation
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Knockdown Techniques
  • Heart/drug effects
  • Heart/embryology
  • Injections
  • Morpholinos/administration & dosage
  • Morpholinos/pharmacology
  • Motor Neurons/cytology
  • Motor Neurons/drug effects
  • Neovascularization, Physiologic/drug effects
  • Neural Crest/drug effects
  • Neural Crest/embryology
  • Otolithic Membrane/drug effects
  • Otolithic Membrane/embryology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Retina/abnormalities
  • Retina/drug effects
  • Retina/embryology
  • Skull/drug effects
  • Skull/embryology
  • Somites/drug effects
  • Spine/drug effects
  • Spine/embryology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
22363697 Full text @ PLoS One

CHARGE syndrome is caused by mutations in the CHD7 gene. Several organ systems including the retina, cranial nerves, inner ear and heart are affected in CHARGE syndrome. However, the mechanistic link between mutations in CHD7 and many of the organ systems dysfunction remains elusive. Here, we show that Chd7 is required for the organization of the neural retina in zebrafish. We observe an abnormal expression or a complete absence of molecular markers for the retinal ganglion cells and photoreceptors, indicating that Chd7 regulates the differentiation of retinal cells and plays an essential role in retinal cell development. In addition, zebrafish with reduced Chd7 display an abnormal organization and clustering of cranial motor neurons. We also note a pronounced reduction in the facial branchiomotor neurons and the vagal motor neurons display aberrant positioning. Further, these fish exhibit a severe loss of the facial nerves. Knock-down of Chd7 results in a curvature of the long body axis and these fish develop irregular shaped vertebrae and have a reduction in bone mineralization. Chd7 knockdown also results in a loss of proper segment polarity illustrated by flawed efnb2a and ttna expression, which is associated with later vascular segmentation defects. These critical roles for Chd7 in retinal and vertebral development were previously unrecognized and our results provide new insights into the role of Chd7 during development and in CHARGE syndrome pathogenesis.

Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes