Ptk7 Is Dynamically Localized at Neural Crest Cell–Cell Contact Sites and Functions in Contact Inhibition of Locomotion

Anita Grund,Klaudia Giehl,Katharina Till,Annette Borchers

doi:10.3390/ijms22179324

Anita Grund, Klaudia Giehl + Show 2 more

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https://doi.org/10.3390/ijms22179324

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Abstract

Neural crest (NC) cells are highly migratory cells that contribute to various vertebrate tissues, and whose migratory behaviors resemble cancer cell migration and invasion. Information exchange via dynamic NC cell–cell contact is one mechanism by which the directionality of migrating NC cells is controlled. One transmembrane protein that is most likely involved in this process is protein tyrosine kinase 7 (PTK7), an evolutionary conserved Wnt co-receptor that is expressed in cranial NC cells and several tumor cells. In Xenopus, Ptk7 is required for NC migration. In this study, we show that the Ptk7 protein is dynamically localized at cell–cell contact zones of migrating Xenopus NC cells and required for contact inhibition of locomotion (CIL). Using deletion constructs of Ptk7, we determined that the extracellular immunoglobulin domains of Ptk7 are important for its transient accumulation and that they mediate homophilic binding. Conversely, we found that ectopic expression of Ptk7 in non-NC cells was able to prevent NC cell invasion. However, deletion of the extracellular domains of Ptk7 abolished this effect. Thus, Ptk7 is sufficient at protecting non-NC tissue from NC cell invasion, suggesting a common role of PTK7 in contact inhibition, cell invasion, and tissue integrity.

Highlights

The neural crest (NC) is an excellent model system used to study signaling mechanisms that guide cell migration
Xenopus embryos were injected with protein tyrosine kinase 7 (PTK7)-GFP RNA in combination with RNA coding for H2Bmcherrry to track the nuclei of migrating NC cells
NC explants were dissected at premigratory NC cell stages, cultured on fibronectin, and NC cell migration was analyzed by time lapse imaging using spinning disk microscopy

Summary

Introduction

The neural crest (NC) is an excellent model system used to study signaling mechanisms that guide cell migration. Multiple pathways and transcription factors, such as SNAIL and TWIST mediate this transition in NC and cancer cells [6,7] Both cell types express matrix metalloproteases to enable cells to adopt an invasive phenotype. This motile phenotype is characterized by planar cell polarity (PCP) [8], which is regulated by a non-canonical Wnt signaling pathway. In this context, it was shown that PCP signaling plays a role in contact inhibition of locomotion (CIL), a phenomenon whereby cells change their directionality after cell–cell contact [9,10]

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