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Genetic analysis of Pitx2 function in zebrafish development
Author(s) -
Ji Yongchang,
Amack Jeffrey
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.872.5
Subject(s) - pitx2 , zebrafish , homeobox , biology , transcription factor , eye development , morphogenesis , mutant , genetics , gene , microbiology and biotechnology
Pitx2 is a homeodomain transcription factor that is highly conserved in vertebrates. Mutations in Pitx2 cause autosomal dominant Axenfeld‐Rieger syndrome (ARS), characterized by eye and tooth malformations. In addition, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates formation of left‐right (LR) asymmetries in the heart and gut. Pitx2 is thought to mediate asymmetric morphogenesis of these organs, but functional studies in animal models have revealed inconsistencies. To gain new insight into Pitx2 function we have used genome editing to create mutations in zebrafish pitx2. We targeted the homeodomain (HD) to disrupt both pitx2a and pitx2c isoforms or the first exon of pitx2c to generate pitx2c‐specific mutations. Surprisingly, pitx2HD‐/‐ and pitx2c‐/‐ mutants showed no gross malformations during the first 7 days of development and many survived to adulthood. Eye defects were then observed in pitx2HD‐/‐, but not pitx2c‐/‐, adults. Further analyses revealed aberrant development of the cornea and anterior chamber of the eye and reduced or absent pharyngeal teeth in pitx2HD‐/‐ mutant embryos, which are defects reminiscent of ARS. Intriguingly, LR asymmetries of the heart and gut developed normally in pitx2HD‐/‐ and pitx2c‐/‐ mutants. These findings suggest conserved roles for Pitx2 in eye and tooth development and reveal Pitx2 is dispensable for LR development in zebrafish.