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P.J. Gage, S.K. Pruckha, W. Rhoades; Fate Maps of Neural Crest and Mesoderm in the Mammalian Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1085.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Multiple ocular tissues required for normal visual function derive embryonically from the periocular mesenchyme. In addition, instructive cues from the mesenchyme are required for correct patterning and differentiation of the optic cup and stalk. Fate mapping in birds demonstrated that the periocular mesenchyme receives contributions from both neural crest and mesoderm. Although these results have served as a model for mammalian eye development, significant differences may exist. We have now constructed detailed fate maps of neural crest and mesoderm in a mammal. Methods: A binary transgenic system consisting of a Wnt1Cre transgene and the ROSA26 Cre reporter gene was used to indelibly mark neural crest lineages by genetic activation of a lacZ cassette. In an analogous system, a αGsuCre transgene was used with the reporter gene to mark mesoderm lineages. Marked cell lineages were detected by immunostaining with anti-ßgal antibodies. Key mesenchymal markers including PITX2 were also detected by immunohistochemistry. Results: Neural crest and mesoderm precursors are present in the eye field by e10.5 as largely distinct cell populations. Pitx2 is expressed in both neural crest and mesodermal lineages but appears to be activated by distinct mechanisms in each cell type. Extensive mixing of the two cell lineages occurs by e12.5. Multiple ocular structures derived from mesenchyme receive contributions from both neural crest. This includes tissues that are derived solely from one precursor type or the other in birds. However, each precursor type contributes specific cell lineages within these chimeric tissues. Conclusions: We have used binary transgenic systems to determine the fates of ocular neural crest and mesoderm in mice as a model for the distribution of these two embryonic precursor lineages in mammalian eyes. The contributions of each precursor to ocular structures is complex, with multiple tissues containing certain cell lineages derived from neural crest while other lineages are derived from mesoderm. These results provide an essential foundation for understanding normal and abnormal eye development.
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