Expression profiling during ocular development identifies two nlz genes with a critical role in fissure closure
Thesis (Ph.D.)--Georgetown University, 2008.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. The optic fissure is a transient structure in the ventral eye during vertebrate eye development. Failure of the optic fissure to close can lead to coloboma, a gap in the ventral eye. This can be a severely debilitating and blinding malformation in humans. The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. Here we use a global approach to profile gene expression during optic fissure closure using laser capture microdissected tissue from the margins of the fissure. From these data, we identify a novel role for the zinc finger-containing proteins Nlz1 and Nlz2 in normal fissure closure. Gene knockdown of nlz1 and nlz2 in zebrafish leads to a failure of the optic fissure to close, a phenotype which closely resembles that seen in human uveal coloboma. We also identify a novel interaction between the Nlz proteins and Pax2 in the developing eye and observe that Nlz1 and Nlz2 appear to act upstream of Pax2 pathway in directing proper closure of the optic fissure.
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Christian, Michael D.; Hawryluck, Laura; Wax, Randy S.; Cook, Tim; Lazar, Neil M.; Herridge, Margaret S.; Muller, Matthew P.; Gowans, Douglas R.; Fortier, Wendy; Burkle, Frederick M., Jr. (2006-11-21)