Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions.

Jason A Morrison,Samuel Meier,Andrew C Box,Rebecca Mclennan,Paul M Kulesa,Hua Li,Craig L Semerad,Anoja G Perera,Jessica M Teddy,Madelaine M Gogol,Mary C Mckinney,Kathryn E Hall,Lauren A Wolfe,Laura Holmes

doi:10.7554/elife.28415

Abstract

Neural crest cells migrate throughout the embryo, but how cells move in a directed and collective manner has remained unclear. Here, we perform the first single-cell transcriptome analysis of cranial neural crest cell migration at three progressive stages in chick and identify and establish hierarchical relationships between cell position and time-specific transcriptional signatures. We determine a novel transcriptional signature of the most invasive neural crest Trailblazer cells that is consistent during migration and enriched for approximately 900 genes. Knockdown of several Trailblazer genes shows significant but modest changes to total distance migrated. However, in vivo expression analysis by RNAscope and immunohistochemistry reveals some salt and pepper patterns that include strong individual Trailblazer gene expression in cells within other subregions of the migratory stream. These data provide new insights into the molecular diversity and dynamics within a neural crest cell migratory stream that underlie complex directed and collective cell behaviors.

Highlights

IntroductionSignals within the dorsal neural tube and microenvironments through which neural crest cells travel direct cells in multicellular, discrete streams to precise peripheral targets
Neural crest migration is crucial to vertebrate organogenesis
Bulk RNA-seq analysis affirms a rich diversity of gene expression between the invasive front and remainder of the neural crest cell migratory stream

Summary

Introduction

Signals within the dorsal neural tube and microenvironments through which neural crest cells travel direct cells in multicellular, discrete streams to precise peripheral targets. Time-lapse analyses have captured the complexity of neural crest cell behaviors that include the transition from the dorsal neural tube to directed migration and movement in collective groups. Cell morphologies and behaviors appear to vary depending on cell position within a migratory stream. Despite these observations at the population level, our understanding of how migrating neural crest cells interpret and respond to microenvironmental signals at the molecular level and coordinate their behaviors remains poorly understood. There is a tremendous need to interrogate the genomic features of migrating neural crest cells in a spatial and temporal manner with the goal of elucidating the underlying mechanisms of directed and collective cell migration

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