Protein Tyrosine Phosphatase 4A3 (PTP4A3) Is Required for Xenopus laevis Cranial Neural Crest Migration In Vivo

Selma Maacha,Océane Anezo,Caterina Pegoraro,Simon Saule,Nathalie Planque,Anne H Monsoro-Burq,Cécile Laurent,Frédérique Maczkowiak

doi:10.1371/journal.pone.0084717

Abstract

Uveal melanoma is the most common intraocular malignancy in adults, representing between about 4% and 5% of all melanomas. High expression levels of Protein Tyrosine Phosphatase 4A3, a dual phosphatase, is highly predictive of metastasis development and PTP4A3 overexpression in uveal melanoma cells increases their in vitro migration and in vivo invasiveness. Melanocytes, including uveal melanocytes, are derived from the neural crest during embryonic development. We therefore suggested that PTP4A3 function in uveal melanoma metastasis may be related to an embryonic role during neural crest cell migration. We show that PTP4A3 plays a role in cephalic neural crest development in Xenopus laevis. PTP4A3 loss of function resulted in a reduction of neural crest territory, whilst gain of function experiments increased neural crest territory. Isochronic graft experiments demonstrated that PTP4A3-depleted neural crest explants are unable to migrate in host embryos. Pharmacological inhibition of PTP4A3 on dissected neural crest cells significantly reduced their migration velocity in vitro. Our results demonstrate that PTP4A3 is required for cephalic neural crest migration in vivo during embryonic development.

Highlights

Uveal melanoma (UM), which results from a malignant transformation of uveal melanocytes, is the most common intraocular malignancy in adults
whole-mount in situ hybridization (WISH) was conducted on stage 17-dissected neural crest (NC) explants to unambiguously demonstrate xlPTP4A3 expression in the NC. xlPTP4A3 (Figure 1, L), and the NC marker xlSNAI2 were expressed in the NC explants but no signal was observed with the sense control probe (Figure 1, L’)
These results demonstrate that xlPTP4A3 is expressed in NC territory during Xenopus laevis development

Summary

Introduction

Uveal melanoma (UM), which results from a malignant transformation of uveal melanocytes (located in the iris, ciliary body and choroid), is the most common intraocular malignancy in adults. Gene expression profiling (GEP) or transcriptomic analysis studies have identified two major subgroups of UM, one of low and one of high metastatic potential [3]. Using these transcriptomic approaches, we previously showed that high expression of PTP4A3 called PRL-3 (Protein Tyrosine Phosphatase 4A3/ Protein of Regenerating Liver-3), a dual phosphatase encoding gene [4], is predictive of metastasis development [5]. PTP4A3 overexpression in UM cells increased their in vitro migration and in vivo invasiveness [1]

Methods

Results

Conclusion