Smith, Alexa; (1997) Functional Analysis Of Receptor Tyrosine Kinases Sek1 And Elk In Neural Crest In The Xenopus Embryo. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Segmentation underlies patterning of the hindbrain and of the branchial neural crest which migrates from the hindbrain to form skeletal components in the visceral arches. Branchial neural crest cells migrate in three streams to specific visceral arches, and since their anteroposterior identity is to some extent prepatterned, it is important that they migrate to the correct arch. Based on their spatially restricted expression several Eph-related receptor tyrosine kinases (RTKs) may be involved in patterning of the branchial neural crest. Recent work has identified a family of polypeptide ligands for these RTKs. I have analysed the expression and function of two Eph-related receptors, Sek1 and Elk which are expressed in a subset of neural crest. SeK1 mRNA is first detected in branchial neural crest adjacent to rhombomere 5 and persists as these cells migrate into the third arch. Prior to migration there is also a ventral domain of expression in the mesoderm which may be the presumptive future migration pathway of this neural crest. Elk mRNA is first detected throughout the presumptive branchial neural crest, and continues in crest cells migrating into the third and fourth arches. In addition there is ventral mesodermal Elk expression in the third and fourth arches. These expression patterns suggest that Sek1 and Elk may mediate cell interactions during branchial neural crest migration. Previous studies have suggested a role of Sek1 in restricting cell movement between rhombomeres. I have taken a dominant negative approach and expressed truncated Sek1 and Elk receptor in Xenopus embryos to investigate their roles in neural crest. Analysis of the resulting embryos with a variety of neural crest markers showed abnormal migration of third arch neural crest cells into adjacent territories. A ligand for Sek1 and Elk, Htk-L, was found to be expressed in the second arch neural crest, which is complementary to the expression of Sek1 and Elk. Overexpression of Htk-L lead to aberrant migration of third arch neural crest into the adjacent territories. These results together with the expression data indicate that the receptors and ligands may mediate a cell repulsion that restricts neural crest cell migration to the correct destination. Since recent work has implicated Eph RTKs and their ligands in axon guidance, this indicates that common mechanisms may be used for regulating the migration of neural crest and axons.

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