title: Role of Chd7 in zebrafish: a model for CHARGE syndrome.
abstract: 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.
authors.affiliation: Sainte-Justine Hospital Research Center, Montreal, Quebec, Canada.
authors.forename: Shunmoogum A
authors.initials: SA
authors.lastname: Patten
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Jacobs-McDaniels
authors.forename: Charlotte
authors.initials: C
authors.lastname: Zaouter
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: R Craig
authors.initials: RC
authors.lastname: Albertson
authors.forename: Florina
authors.initials: F
authors.lastname: Moldovan
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D058747:CHARGE Syndrome / Q000235:genetics / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D005145:Face / Q000294:innervation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006321:Heart / Q000187:drug effects / Q000196:embryology; D007267:Injections; D060172:Morpholinos / Q000008:administration & dosage / Q000494:pharmacology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009432:Neural Crest / Q000187:drug effects / Q000196:embryology; D010037:Otolithic Membrane / Q000187:drug effects / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D012886:Skull / Q000187:drug effects / Q000196:embryology; D019170:Somites / Q000187:drug effects; D013131:Spine / Q000187:drug effects / Q000196:embryology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D060172:Morpholinos; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D004265:DNA Helicases; C569452:Chd7 protein, zebrafish