WNT Takes Centre Stage in Border Control

Those who follow politics know that the borders between countries regulated suggesting that WNTs could be decisive for NPB fate acquisican cause disagreements and sometimes evenwar, and that border control is an ongoing source of controversy. A different—but not less controversial—border is established during embryogenesis in vertebrates: the neural plate border (NPB) that separates neural and nonneural ectoderm (Streit and Stern, 1999; Patthey and Gunhaga, 2011; Groves and LaBonne, 2014). A study in this issue of EbioMedicine implicates WNT signalling in cell specification in this region and, for the first time, links this signalling pathway to the emergence of neural tube defects (NTDs) (Kimura-Yoshida et al., 2015–in this issue). The neural plate is a sheet of pseudostratified epithelium in the centre of the ectoderm (the outermost layer of an embryo) that goes on to generate the central nervous system. It is surrounded by non-neural surface ectoderm (SE) that goes on to form the outer covering of the organism, the epidermis. Shortly after neural plate formation, its longitudinal midline dips in, resulting in lateral elevation of the neural folds. Subsequently these neural folds roll inwards, and the NPBs from the opposite sides of the neural plate meet and fuse, thereby forming the neural tube. If this process, neurulation, is defective, NTDs such as craniorachischisis, anencephaly and spina bifida can ensue (Greene and Copp, 2014). However, the importance of the NPB reaches further than just functioning as a zipper during neurulation as this region also gives rise to the neural crest, amultipotent cell population thatmigrates to different parts of the embryo and contributes to various organs and tissues. How exactly neural crest cells become specified has been a bone of contention for some time (Schlosser, 2008; Weston and Thiery, 2015; Simões-Costa and Bronner, 2015). Enter Kimura-Yoshida et al. who have studied NPB specification in the mouse embryo and found that this region contains a stripe of cells that until neural tube closure express neither markers of the neural plate nor markers of the SE, but instead known markers of stem cell identity. Neural crest cells are often considered ‘stem cell-like’, but only minimal overlap was found between the uncommitted NPB cells and a neural crest marker, indicating that these two populations are distinct. Upon neural tube closure NPB cells finally become specified as either neural or epidermal. In order to identify candidate molecular signals that may bring about this decision, Kimura-Yoshida et al. microdissected neural plate and SE tissue and compared their respective gene expression profiles using DNA microarray analysis. A striking number of factors of the WNT signalling pathway were found to be differentially