Angiopoietin 2 signaling plays a critical role in neural crest cell migration.

Mary Cathleen Mckinney,Paul M Kulesa,Rebecca Mclennan

doi:10.1186/s12915-016-0323-9

Mary Cathleen Mckinney, Paul M Kulesa + Show 1 more

Open Access

https://doi.org/10.1186/s12915-016-0323-9

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Abstract

BackgroundCollective neural crest cell migration is critical to the form and function of the vertebrate face and neck, distributing bone, cartilage, and nerve cells into peripheral targets that are intimately linked with head vasculature. The vasculature and neural crest structures are ultimately linked, but when and how these patterns develop in the early embryo are not well understood.ResultsUsing in vivo imaging and sophisticated cell behavior analyses, we show that quail cranial neural crest and endothelial cells share common migratory paths, sort out in a dynamic multistep process, and display multiple types of motion. To better understand the underlying molecular signals, we examined the role of angiopoietin 2 (Ang2), which we found expressed in migrating cranial neural crest cells. Overexpression of Ang2 causes neural crest cells to be more exploratory as displayed by invasion of off-target locations, the widening of migratory streams into prohibitive zones, and differences in cell motility type. The enhanced exploratory phenotype correlates with increased phosphorylated focal adhesion kinase activity in migrating neural crest cells. In contrast, loss of Ang2 function reduces neural crest cell exploration. In both gain and loss of function of Ang2, we found disruptions to the timing and interplay between cranial neural crest and endothelial cells.ConclusionsTogether, these data demonstrate a role for Ang2 in maintaining collective cranial neural crest cell migration and suggest interdependence with endothelial cell migration during vertebrate head patterning.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0323-9) contains supplementary material, which is available to authorized users.

Highlights

Collective neural crest cell migration is critical to the form and function of the vertebrate face and neck, distributing bone, cartilage, and nerve cells into peripheral targets that are intimately linked with head vasculature
It makes logical sense that trailing neural crest cells maintain a diffusive behavior that is regulated by angiopoietin 2 (Ang2) signaling in order to promote collective cell migration. To our knowledge, these data represent the first report of the critical function of Ang2 during collective neural crest cell migration and detailed characterization of the spatio-temporal dynamics of neural crest and endothelial cells during vertebrate head patterning
Our hypothesis of the role of Ang2 to promote neural crest migration supported by these results fits well with our previously proposed cell-induced gradient model [39, 40] in which lead cells read out guidance cues and transfer information to trailing cells

Summary

Introduction

Collective neural crest cell migration is critical to the form and function of the vertebrate face and neck, distributing bone, cartilage, and nerve cells into peripheral targets that are intimately linked with head vasculature. Morphogenesis of the vertebrate head involves the close coordination of multiple cell populations that build tissue structures of the face and neck. One example of this is the intimate patterning of neural crest-derived tissues with vasculature. Neural crest cells are highly migratory, emigrate from the dorsal neural tube to peripheral locations along stereotypical migratory pathways, and contribute to multiple tissues. Studies that examine neural crest and endothelial cell dynamics and underlying molecular choreography would help us better understand vertebrate head patterning

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