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DC Baulmann, A Ohlmann, C Flugel-Koch, S Goswami, A Cvekl, ER Tamm; Pax6 Activity is Required for Formation of Schlemm's Canal and Differentiation of the Trabecular Meshwork . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1023.
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Purpose: To examine the anterior eye segment phenotype of heterozygous Pax6lacZ/+ mutant mice (St-Onge et al. 1997) and to study the role of Pax6 for the development of trabecular meshwork (TM) and Schlemm's canal. Methods: Eyes of heterozygous Pax6lacZ/+ mutant mice from postnatal day (P)1 to 6 weeks of age were investigated by light and electron microscopy. Activity of the lacZ reporter gene was visualized by ß-gal staining. Pax6 expression was analyzed in a murine TM cell line (MUTM-NEI/1) by RT-PCR and western blotting of nuclear proteins. Results: Mesenchymal cells of presumably neural crest origin were seen in the chamber angle of wildtype and mutant mice at P1 to P3. In wildtype mice, these cells differentiated until P14 into typical TM cells covering connective tissue lamellae next to Schlemm's canal. In heterozygous Pax6lacZ/+ mutant mice, TM cells remained in an undifferentiated mesenchymal state and Schlemm's canal did not form. From P1 to P4, activity of the reporter gene was observed in ocular cells of ectodermal and neuroepithelial origin and, at weaker intensity, in mesenchymal cells within the chamber angle region. Similar staining was seen in other cell types of neural crest origin such as that of the iris stroma, corneal stroma and endothelium. No staining was seen in control eyes. At later stages, ß-gal staining was still present in ocular cells of ectodermal and neuroepithelial origin, but was absent in ocular cells of neural crest origin. Cultured murine TM cells expressed Pax6. Conclusion: Pax6 activity is required for the formation of Schlemm's canal and the proper differentiation of the TM. Pax6 promoter activity in TM cells and other ocular cells of neural crest origin during early postnatal life indicates that Pax6 may play a direct role for neural crest differentiation during development of the anterior eye.
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