Zebrafish pitx3 is necessary for normal lens and retinal development

Shi, X., Bosenko, D.V., Zinkevich, N.S., Foley, S., Hyde, D.R., Semina, E.V., and Vihtelic, T.S.
Mechanisms of Development   122(4): 513-527 (Journal)
Registered Authors
Hyde, David R., Shi, Xiaohai, Vihtelic, Thomas
Pitx3; Lens; Retina; Zebrafish; Morpholino
MeSH Terms
  • Actins/metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cloning, Molecular
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/genetics
  • Homeodomain Proteins/chemistry
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Humans
  • Immunohistochemistry
  • Lens, Crystalline/embryology*
  • Lens, Crystalline/metabolism*
  • Molecular Sequence Data
  • Phenotype
  • Retina/embryology*
  • Retina/metabolism*
  • Sequence Alignment
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
15804565 Full text @ Mech. Dev.
The human PITX3 gene encodes a bicoid-like homeodomain transcription factor associated with a variety of congenital ocular conditions, including anterior segment dysgenesis, Peter's anomaly, and cataracts. We identified a zebrafish pitx3 gene encoding a protein (Pitx3) that possesses 63% amino acid identity with human PITX3. The zebrafish pitx3 gene encompasses approximately 16.5kb on chromosome 13 and consists of four exons, which is similar to the genomic organization of other pitx genes. Expression of the zebrafish pitx3 gene was studied by in situ mRNA hybridization and RT-PCR. The pitx3 transcripts were detected throughout development with the greatest level of expression occurring in the developing lens and brain at 24hpf. In adults, the highest expression was detected in the eye. Morpholinos were used to knockdown expression of the Pitx3 protein and a control morpholino that contains five mismatched bases was used to confirm the specificity of the phenotypes. The morphants had small eyes, misshapen heads and reduced jaws and fins relative to controls. The morphants exhibited abnormalities in lens development and their retinas contained pyknotic nuclei accompanied by a reduction in the number of cells in different neuronal classes. This suggests the lens is required for retinal development or Pitx3 has an unexpected role in retinal cell differentiation or survival. These results demonstrate zebrafish pitx3 represents a true ortholog of the human PITX3 gene and the general function of the Pitx3 protein in lens development is conserved between mammals and the teleost fish.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes