Requirement for EphA receptor signaling in the segregation of Xenopus third and fourth arch neural crest cells

We describe here the isolation of a full-length cDNA encoding a Xenopus ort hologue of the mammalian EphA2 receptor tyrosine kinase and investigate its role in cranial neural crest migration. We show that the primary sites of Xenopus EphA2 expression are rhombomere 4 of the developing hindbrain, migr atory cranial neural crest cells and mesoderm of the visceral arches. To in terfere with EphA2 and related receptors during cranial neural crest migrat ion, we took a dominant negative approach. Overexpression of kinase-deficie nt EphA2 receptor variants led to abnormal migration of cranial neural cres t cells. Neural crest cells of the third arch were found to mismigrate post eriorly, resulting in the failure of third and fourth arch neural crest to separate into distinct streams. These defects could be rescued by expressio n of full-length EphA2 receptors. A comparison of the expression domains of EphA2-binding proteins mapped by receptor affinity probe (RAP) in situ sta ining with those for EphA2 receptors revealed co-expression of ligands and receptors in the visceral arch mesenchyme. Taken together, these results su ggest that EphA receptors may mediate attractive or adhesive signals during migration of cranial neural crest cells. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.