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A. Kahana, F. Elsaeidi, D. Demiri, B. L. Bohnsack, A.-A. Calinescu, D. Goldman; Retinoic Acid Regulates Orbital Development and Extraocular Muscle Organization in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3037.
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© ARVO (1962-2015); The Authors (2016-present)
Orbital disease can involve reactivation of embryogenic pathways. We aim to utilize a novel zebrafish model of orbital development to evaluate the role of the neural crest in orbital organization.
Zebrafish transgenic strains were used for real-time fluorescence and confocal microscopy to assess orbital development following experimental perturbations to the retinoic acid signaling system, including inhibition of RA synthesis with DEAB. In situ hybridization and immunohistochemistry experiments were used to complement the live microscopy experiments and identify potential targets.
Retinoic acid (RA) is a key morphogen during embryogenesis and a powerful teratogen, and its synthesis is tightly regulated both spatially and temporally. RA is also a key regulator of neural crest development. Evidence from mouse molecular genetics revealed a key role for RA signaling in the regulation of orbital development, although the exact mechanism and key intercellular interactions remain to be discovered. We developed a zebrafish model for studying orbital development utilizing transgenic strains for real-time assessment of extraocular muscles (EOM) and cranial neural crest development, along with ISH and IHC experiments. Using this model, we inhibit retinoic acid synthesis with DEAB beginning at 24hpf and show that EOM differentiate appropriate, but the exact anatomic localization of EOMs around the eye is disrupted (figure).
Zebrafish orbital development reveals a dependence on RA signaling that is very similar to data from existing mammalian models. The zebrafish model allows us to further characterize the key cellular interactions and signaling pathways using live microscopy techniques where cellular microenvironments around the eye can be observed intact. This is a powerful model that has great promise to further our understanding of orbital and extraocular muscle development and disease.
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