DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

Rebecca McLennan, Caleb M. Bailey, Linus J. Schumacher, Jessica M. Teddy, Jason A. Morrison, Jennifer C. Kasemeier-Kulesa, Lauren A. Wolfe, Madeline M. Gogol, Ruth E. Baker, Philip K. Maini, Paul M. Kulesa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling.

Original languageEnglish
Pages (from-to)3339-3354
Number of pages16
JournalJournal of Cell Biology
Volume216
Issue number10
Early online date15 Aug 2017
DOIs
Publication statusPublished - 2 Oct 2017

Keywords

  • LEFT-RIGHT ASYMMETRY
  • CELL-MIGRATION
  • EMBRYONIC MICROENVIRONMENT
  • DEVELOPING CHICK
  • RAT FIBROBLASTS
  • PG-M/VERSICAN
  • GENE-PRODUCT
  • INNER-EAR
  • MELANOMA
  • EXPRESSION

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