Zebrafish pitx3 is necessary for normal lens and retinal development. Mech Dev 2005 Apr;122(4):513-27
Date
04/05/2005Pubmed ID
15804565DOI
10.1016/j.mod.2004.11.012Scopus ID
2-s2.0-15944427842 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
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.
Author List
Shi X, Bosenko DV, Zinkevich NS, Foley S, Hyde DR, Semina EV, Vihtelic TSAuthors
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinNatalya S. Zinkevich PhD Research Scientist I in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ActinsAmino Acid Sequence
Animals
Animals, Genetically Modified
Cloning, Molecular
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Homeodomain Proteins
Humans
Immunohistochemistry
Lens, Crystalline
Molecular Sequence Data
Phenotype
Retina
Sequence Alignment
Zebrafish
Zebrafish Proteins