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Donika Gallina, Dan Kasprick, Phil Kish, Alon Kahana; Pitx3 is Important for Development and Regeneration of the Extraocular Muscles in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2073.
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The Pitx3 paired homeobox gene is important in embryogenesis,including formation of lens and retina, survival of dopaminergicneurons, and skeletal muscle development. We studied the roleof PitX3 in the development and repair of extraocular muscles(EOMs).
We used in situ hybridization to study expression pattern inembryonic and adult extraocular muscles, and in vivo imagingof actin::GFP transgenic fish to test the effect of morpholinoknockdown of PitX3 in embryos.
We found that PitX3 is expressed in EOMs during embryogenesis,and co-localizes with MyoD, a myogenic regulatory factor (Fig1). Morpholino knockdown of Pitx3 revealed a critical role forthis gene in EOM development. Furthermore, PitX3 is highly inducedin a regenerating lateral rectus muscle (Fig 2), and may beinvolved in both inducing the myogenic program and organizingthe regenerating muscle.
We discovered an important role for Pitx3 in EOM development.This role may get recapitulated during adult EOM regenerationfollowing injury. We are currently investigating downstreamtargets of PitX3, including myogenic and extracellular matrixgenes, utilizing transgenic and microarray techniques. Our discoveryunderscores the relationship between embryogenesis and adulttissue repair. The ability of zebrafish to induce EOM regenerationthrough regulated satellite cell expansion, myogenesis, andproper morphogenesis requires further investigation. This researchwill hopefully lead to the development of novel therapies forthe treatment of congenital and acquired strabismus.
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