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TL Belecky-Adams, R Adler; Bone Morphogenetic Proteins (BMPs) in the Differentiation of the Ventral Optic Cup . Invest. Ophthalmol. Vis. Sci. 2002;43(13):825.
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Purpose: We previously reported that blocking BMP signaling in the chick retina resulted in changes in dorso-ventral patterning, accompanied by morphological alterations in the ventral optic cup and changes in ganglion cell axonal pathfinding (Invest. Ophthalmol. Vis. Sci.,42: S734). The purpose of this study was to elucidate the molecular mechanisms underlying these developmental abnormalities. Methods: BMP signaling was blocked in chicken optic cup by overexpressing the BMP-binding protein noggin, by microinjecting on embryonic day 3 either a noggin-encoding RCAS retrovirus, or a noggin-secreting Chinese Hamster Ovary (CHO) cell line. Controls were an alkaline phosphatase-expressing retrovirus, and a parental CHO cell line, respectively. Embryos were fixed at E6 or E8, and the expression of molecular markers was studied by in situ hybridization or immunocytochemistry in whole mounts and sections. Results: Noggin overexpression caused colobomas, agenesis of the pecten (a vascularized structure that protrudes into the chick vitreous), replacement of the ventral RPE by neuroepithelium-like tissue, and ectopic expression in the ventral retina and RPE region of several molecules normally restricted to the optic stalk, such as Pax-2. Ganglion cell axons frequently grew abnormally and failed to enter the optic nerve, which correlated with alterations in guidance molecules such as netrin and R-cadherin. Conclusion: The data are consistent with the hypothesis that BMPs have significant effects on the development of ventral optic cup structures, including closure of the choroid fissure, inhibition of the expression of optic stalk properties in the ventral optic cup, and axonal guidance mediated by the regulation of the expression of molecules involved in axonal pathfinding. Support: This work is supported by NIH grants EYO4859 and 1765, NEI fellowship EYO6642, the Knights Templar Eye Foundation, Inc., Research to Prevent Blindness, Foundation Fighting Blindness and a grant from Mrs. Harry J. Duffy.
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