Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish. PLoS One 2012;7(1):e30896

Date

02/04/2012

Pubmed ID

22303467

Pubmed Central ID

PMC3267762

DOI

10.1371/journal.pone.0030896

Scopus ID

2-s2.0-84856386051 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5) splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5) morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5) morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates.

Author List

Liu Y, Semina EV

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Biomarkers
Craniofacial Abnormalities
Embryo, Nonmammalian
Embryonic Development
Exons
Eye Abnormalities
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Homeodomain Proteins
Humans
In Situ Hybridization
Molecular Sequence Data
Morpholinos
Phenotype
Protein Biosynthesis
RNA Splicing
RNA, Messenger
Transcription Factors
Zebrafish
Zebrafish Proteins