title: Cdc42 and sec10 Are Required for Normal Retinal Development in Zebrafish.
abstract: OBJECTIVE
  To characterize the function and mechanisms of cdc42 and sec10 in eye development in zebrafish.
  
  
  METHODS
  Knockdown of zebrafish cdc42 and sec10 was carried out using antisense morpholino injection. The phenotype of morphants was characterized by histology, immunohistology, and transmission electron microscopy (TEM). To investigate a synergistic genetic interaction between cdc42 and sec10, we titrated suboptimal doses of cdc42 and sec10 morpholinos, and coinjected both morpholinos. To study trafficking, a melanosome transport assay was performed using epinephrine.
  
  
  RESULTS
  Cdc42 and sec10 knockdown in zebrafish resulted in both abnormal eye development and increased retinal cell death. Cdc42 morphants had a relatively normal retinal structure, aside from the absence of most connecting cilia and outer segments, whereas in sec10 morphants, much of the outer nuclear layer, which is composed of the photoreceptor nuclei, was missing and RPE cell thickness was markedly irregular. Knockdown of cdc42 and sec10 also resulted in an intracellular transport defect affecting retrograde melanosome transport. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 act in the same pathway in retinal development.
  
  
  CONCLUSIONS
  We propose a model whereby sec10 and cdc42 play a central role in development of the outer segment of the retinal photoreceptor cell by trafficking proteins necessary for ciliogenesis.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States.
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Baek
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States.
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States 3Department of Medicine, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, United States.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Lipschutz
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D009929:Organ Size; D012160:Retina / Q000196:embryology*; D012162:Retinal Degeneration / Q000503:physiopathology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D033921:Vesicular Transport Proteins; D029961:Zebrafish Proteins; D020764:cdc42 GTP-Binding Protein