Regulation of avian cranial neural crest cell migration by eph receptors and ephrin ligands

dc.contributor.authorMellott, Daniel Owen
dc.contributor.supervisorBurke, Robert D.
dc.date.accessioned2008-06-09T20:00:14Z
dc.date.available2008-06-09T20:00:14Z
dc.date.copyright2006en_US
dc.date.issued2008-06-09T20:00:14Z
dc.degree.departmentDept. of Biologyen_US
dc.degree.levelDoctor of Philosophy Ph.D.en_US
dc.description.abstractEph receptors and their ephrin ligands play important roles in guiding mouse and Xenopus cranial neural crest (CNC) cells to their destinations. My objective was to determine if Ephs and ephrins also regulate avian CNC pathfinding. By double labeling for Eph or ephrin RNA and a neural crest marker protein, I was able to clearly distinguish neural crest from ectoderm and head mesenchyme and show that avian CNC cells express EphA3, 4, and 7 and EphB 1 and 3 and migrate along pathways bordered by non-neural crest cells expressing ephrin-B 1. Surprisingly, avian CNC cells also express ephrin-B2 and migrate along pathways bordered by non-neural crest cells expressing EphB2. Consistent with these findings, explanted avian CNC cells are labeled by both ephrin-B I and EphB2 Fc fusion proteins. Given the choice between growing out onto substrate-bound fibronectin (FN) or FN plus clustered Fc protein in the stripe assay, these cells show no preference for either condition. Conversely, given the choice between FN or FN plus clustered ephrin-B1 or EphB2 Fc fusion protein, the cells strongly localize to stripes containing only FN. This response is mitigated in the presence of soluble ephrin-B1/Fc or EphB2/Fc, but not in the presence of soluble Fc alone. These findings show that avian CNC cells have a mutually exclusive distribution with non-neural crest cells expressing ephrin-B 1 and EphB2 RNA in situ and are repelled from ephrin-B1 and EphB2 protein in vitro, suggesting that their migration is guided by both forward signaling through a variety of Eph receptors as stimulated by ephrin-B1 and reverse signaling through ephrin-B2 as stimulated by EphB2. I further explore the phylogeny of Ephs and ephrins and show that these genes diversified at different times in evolutionary history, such that the ancestral chordate likely had a single receptor for two different ligands.en_US
dc.identifier.urihttp://hdl.handle.net/1828/978
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectbirdsen_US
dc.subjectembryologyen_US
dc.subjectneural cresten_US
dc.subject.lcshUVic Subject Index::Sciences and Engineering::Biology::Neurosciencesen_US
dc.subject.lcshUVic Subject Index::Sciences and Engineering::Biologyen_US
dc.titleRegulation of avian cranial neural crest cell migration by eph receptors and ephrin ligandsen_US
dc.typeThesisen_US

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