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Published March 1997 | public
Journal Article

Eph Family Transmembrane Ligands Can Mediate Repulsive Guidance of Trunk Neural Crest Migration and Motor Axon Outgrowth


In vertebrate embryos, neural crest cell migration and motor axon outgrowth are restricted to rostral somite halves by repulsive factors located in the caudal somite compartment. We show that two Eph family transmembrane ligands, Lerk2 and HtkL, are expressed in caudal somite halves, and that crest cells and motor axons express receptors for these ligands. In several independent in vitro assays, preclustered ligand-Fc fusion proteins can repulsively guide both crest migration and motor axon outgrowth. These repulsive activities depend on a graded or discontinuous presentation of the ligands when tested in the context of permissive substrates, such as laminin or fibronectin. These results identify Lerk2 and HtkL as potential determinants of segmental pattern in the peripheral nervous system.

Additional Information

© 1997 by Cell Press. Under an Elsevier user license. Received December 27, 1996; revised January 24, 1997. We thank A. Groves and N. Shah for teaching the in situ hybridization and neural crest explant procedures, respectively; S. Fashena for the hIgG1-Fc vector; L. Lo for anti-c-ret antibody; T. Frankfurter for TUJ1 antibody; J. Lauder and J. Moiseiwitsch for advice on the chemotaxis assay; J. Vielmetter and C. Krull for advice on the stripe assay, and C. Marcelle for help in the interpretation of the chick in situs. We are particularly grateful to F. Bonhoeffer for providing silicone matrices for use in the stripe assays. We thank N. Gale and G. Yancopoulos for sharing unpublished results, and S. Kulkarni, T. Pawson, and R. Klein for Nuk/Sek4 mutant embryos. We also thank D. Wilkinson, S. Fraser, and M. Bronner-Fraser for communicating their unpublished results and for comments on the manuscript, and our lab members for discussions and support. D. J. A. is an Investigator of the Howard Hughes Medical Institute.

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