VEGF signals induce trailblazer cell identity that drives neural crest migration

Rebecca McLennan, Linus J. Schumacher, Jason A. Morrison, Jessica M. Teddy, Dennis A. Ridenour, Andrew C. Box, Craig L Semerad, Hua Li, William McDowell, David Kay, Philip K. Maini, Ruth E. Baker, Paul M. Kulesa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Embryonic neural crest cells travel in discrete streams to precise locations throughout the head and body. We previously showed that cranial neural crest cells respond chemotactically to vascular endothelial growth factor (VEGF) and that cells within the migratory front have distinct behaviors and gene expression. We proposed a cell-induced gradient model in which lead neural crest cells read out directional information from a chemoattractant profile and instruct trailers to follow. In this study, we show that migrating chick neural crest cells do not display distinct lead and trailer gene expression profiles in culture. However, exposure to VEGF in vitro results in the upregulation of a small subset of genes associated with an in vivo lead cell signature. Timed addition and removal of VEGF in culture reveals the changes in neural crest cell gene expression are rapid. A computational model incorporating an integrate-and-switch mechanism between cellular phenotypes predicts migration efficiency is influenced by the timescale of cell behavior switching. To test the model hypothesis that neural crest cellular phenotypes respond to changes in the VEGF chemoattractant profile, we presented ectopic sources of VEGF to the trailer neural crest cell subpopulation and show diverted cell trajectories and stream alterations consistent with model predictions. Gene profiling of trailer cells that diverted and encountered VEGF revealed upregulation of a subset of 'lead' genes. Injection of neuropilin1 (Np1)-Fc into the trailer subpopulation or electroporation of VEGF morpholino to reduce VEGF signaling failed to alter trailer neural crest cell trajectories, suggesting trailers do not require VEGF to maintain coordinated migration. These results indicate that VEGF is one of the signals that establishes lead cell identity and its chemoattractant profile is critical to neural crest cell migration.

Original languageEnglish (US)
Pages (from-to)12-25
Number of pages14
JournalDevelopmental Biology
Volume407
Issue number1
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Fingerprint

Neural Crest
Vascular Endothelial Growth Factor A
Chemotactic Factors
Up-Regulation
Genes
Phenotype
Gene Expression
Morpholinos
Electroporation
Transcriptome
Cell Movement
Head
Injections
Lead

Keywords

  • Cell migration
  • Chick
  • Computational modeling
  • Embryonic microenvironment
  • Gene expression
  • Molecular profile
  • Neural crest
  • Trailblazers

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

McLennan, R., Schumacher, L. J., Morrison, J. A., Teddy, J. M., Ridenour, D. A., Box, A. C., ... Kulesa, P. M. (2015). VEGF signals induce trailblazer cell identity that drives neural crest migration. Developmental Biology, 407(1), 12-25. https://doi.org/10.1016/j.ydbio.2015.08.011

VEGF signals induce trailblazer cell identity that drives neural crest migration. / McLennan, Rebecca; Schumacher, Linus J.; Morrison, Jason A.; Teddy, Jessica M.; Ridenour, Dennis A.; Box, Andrew C.; Semerad, Craig L; Li, Hua; McDowell, William; Kay, David; Maini, Philip K.; Baker, Ruth E.; Kulesa, Paul M.

In: Developmental Biology, Vol. 407, No. 1, 01.11.2015, p. 12-25.

Research output: Contribution to journalArticle

McLennan, R, Schumacher, LJ, Morrison, JA, Teddy, JM, Ridenour, DA, Box, AC, Semerad, CL, Li, H, McDowell, W, Kay, D, Maini, PK, Baker, RE & Kulesa, PM 2015, 'VEGF signals induce trailblazer cell identity that drives neural crest migration' Developmental Biology, vol. 407, no. 1, pp. 12-25. https://doi.org/10.1016/j.ydbio.2015.08.011
McLennan R, Schumacher LJ, Morrison JA, Teddy JM, Ridenour DA, Box AC et al. VEGF signals induce trailblazer cell identity that drives neural crest migration. Developmental Biology. 2015 Nov 1;407(1):12-25. https://doi.org/10.1016/j.ydbio.2015.08.011
McLennan, Rebecca ; Schumacher, Linus J. ; Morrison, Jason A. ; Teddy, Jessica M. ; Ridenour, Dennis A. ; Box, Andrew C. ; Semerad, Craig L ; Li, Hua ; McDowell, William ; Kay, David ; Maini, Philip K. ; Baker, Ruth E. ; Kulesa, Paul M. / VEGF signals induce trailblazer cell identity that drives neural crest migration. In: Developmental Biology. 2015 ; Vol. 407, No. 1. pp. 12-25.
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