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Neural crest (NC) cell migration is crucial to the formation of peripheral tissues during vertebrate development. However, how NC cells respond to different microenvironments to maintain persistence of direction and cohesion in multicellular streams remains unclear. To address this, we profiled eight subregions of a typical cranial NC cell migratory stream. Hierarchical clustering showed significant differences in the expression profiles of the lead three subregions compared with newly emerged cells. Multiplexed imaging of mRNA expression using fluorescent hybridization chain reaction (HCR) quantitatively confirmed the expression profiles of lead cells. Computational modeling predicted that a small fraction of lead cells that detect directional information is optimal for successful stream migration. Single-cell profiling then revealed a unique molecular signature that is consistent and stable over time in a subset of lead cells within the most advanced portion of the migratory front, which we term trailblazers. Model simulations that forced a lead cell behavior in the trailing subpopulation predicted cell bunching near the migratory domain entrance. Misexpression of the trailblazer molecular signature by perturbation of two upstream transcription factors agreed with the in silico prediction and showed alterations to NC cell migration distance and stream shape. These data are the first to characterize the molecular diversity within an NC cell migratory stream and offer insights into how molecular patterns are transduced into cell behaviors.

Original publication

DOI

10.1242/dev.117507

Type

Journal article

Journal

Development

Publication Date

01/06/2015

Volume

142

Pages

2014 - 2025

Keywords

Cell migration, Chicken, Mathematical modeling, Molecular profiling, Neural crest, Numerical simulation, Single cell, Animals, Avian Proteins, Cell Movement, Chick Embryo, Computer Simulation, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Neural Crest, Polymerase Chain Reaction, RNA, Messenger, Single-Cell Analysis