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Leukocyte Receptor Tyrosine Kinase interacts with secreted midkine to promote survival of migrating neural crest cells

Vieceli, Felipe Monteleone and Bronner, Marianne E. (2018) Leukocyte Receptor Tyrosine Kinase interacts with secreted midkine to promote survival of migrating neural crest cells. Development, 145 (20). Art. No. dev164046. ISSN 0950-1991.

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Neural crest cells migrate long distances throughout the embryo and rely on extracellular signals that attract, repel and/or stimulate survival to ensure proper contribution to target derivatives. Here, we show that leukocyte receptor tyrosine kinase (LTK), an ALK-type receptor tyrosine kinase, is expressed by neural crest cells during early migratory stages in chicken embryos. Loss of LTK in the cranial neural crest impairs migration and results in increased levels of apoptosis. Conversely, midkine, previously proposed as a ligand for ALK, is secreted by the non-neural ectoderm during early neural crest migratory stages and internalized by neural crest cells in vivo. Similar to loss of LTK, loss of midkine reduces survival of the migratory neural crest. Moreover, we show by proximity ligation and co-immunoprecipitation assays that midkine binds to LTK. Taken together, these results suggest that LTK in neural crest cells interacts with midkine emanating from the non-neural ectoderm to promote cell survival, revealing a new signaling pathway that is essential for neural crest development.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Vieceli, Felipe Monteleone0000-0001-5142-8224
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2018 Published by The Company of Biologists Ltd. Received February 6, 2018; Accepted September 13, 2018; Published 18 September 2018. We thank Marcos Simões-Costa and Stephen Roberts for kindly sharing reagents, Narmada Thayapran for technical assistance, and Yuwei Li for valuable comments on the manuscript. The authors declare no competing or financial interests. Author contributions: Conceptualization: F.M.V., M.E.B.; Methodology: F.M.V.; Formal analysis: F.M.V.; Investigation: F.M.V.; Data curation: F.M.V.; Writing - original draft: F.M.V., M.E.B.; Writing - review & editing: F.M.V., M.E.B.; Visualization: F.M.V.; Supervision: M.E.B.; Funding acquisition: F.M.V., M.E.B. This work was supported by a National Institutes of Health grant (R01DE024157 to M.E.B.) and postdoctoral fellowships from the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico) (CNPq PDE 207656/2014-2 to F.M.V.) and the Shurl and Kay Curci Foundation (to F.M.V.). Deposited in PMC for release after 12 months. Supplementary information: Supplementary information available online at
Funding AgencyGrant Number
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)PDE 207656/2014-2
Surl and Kay Curci FoundationUNSPECIFIED
Subject Keywords:neural crest, LTK, midkine, cell survival, apoptosis
Record Number:CaltechAUTHORS:20180924-132214153
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Official Citation:Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote survival of migrating neural crest cells. Felipe Monteleone Vieceli, Marianne E. Bronner. Development 2018 145: dev164046 doi: 10.1242/dev.164046. Published 24 October 2018
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89889
Deposited By: Tony Diaz
Deposited On:24 Sep 2018 22:57
Last Modified:30 Oct 2018 17:46

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