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The Role of EPHB3 in a Human Model of Neural Crest Development and Palate Formation


The Neural Crest (NC) is a population of cells unique to vertebrates that arise early in development, migrate extensively and differentiate into a wide variety of derivatives. Neural crest cells (NCC) give rise to a majority of the connective and skeletal tissues that make up the craniofacial structure including bone, cartilage, melanocytes and other derivatives. To form this intricate three-dimensional structure NCC development must be spatiotemporally accurate. As a result, NCC defects are often evident in the craniofacial region, such as cleft palate. Oral clefts occur in about 1 in every 700 live births and have functional and social implications for the child, including the ability to feed, and speak.

A number of secreted signals have been shown to be involved in NCC development; however, the cell-cell contact signal EPH-EFN has not been widely studied. EPH-EFN is important for other aspects of development and there is evidence from mouse models of oral clefts that it is involved in NCC development. To study the role of EPH-EFN signaling in this process we used an in vitro model of human neural crest development and developed an in vitro model of palate fusion. Better understanding of EPH-EFN in this context could provide us with a number of benefit. An in vitro fusion model, such as the one we have engineered in our lab using a NCC-derived osteoblast core surrounded with an epithelial layer, will allow for an effective, animal free method to study fusion events, including the role of EPH and EFN.

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