Vagal NC cells, which are located between somites 1–7, are marked by the expression of HOX PG(3-5) members ( Kam and Lui, 2015 Fu et al., 2003 Chan et al., 2005) and generate the enteric nervous system (ENS) ( Le Douarin and Teillet, 1973). The latter also includes cells contributing to heart structures (termed cardiac NC) ( Le Douarin et al., 2004 Kirby et al., 1983). dermis, cartilage, bone), melanocytes, neurons and glia colonizing the head ( Le Douarin et al., 2004) and are divided into an anterior HOX-negative and a posterior HOX PG (1-3 )-positive domain. Cranial NC cells give rise to mesoectodermal derivatives (e.g. The identity of NC products correlates with their position along the anteroposterior (A-P) axis, which is in turn reflected by the expression of HOX gene paralogous groups (PGs). Once specified, NC cells undergo epithelial-to-mesenchymal transition (EMT), exit the neural tube, and migrate to generate various cell types. This occurs via the action, first of neural plate border-specific transcription factors such as PAX3/7, MSX and ZIC family members, and then via definitive NC-specifiers (e.g. Studies utilising chick and amphibian embryos have indicated that different levels of BMP, WNT and FGF signals, emanating from the mesoderm/non-neural ectoderm, orchestrate NC induction and specification ( Stuhlmiller and García-Castro, 2012). The neural crest (NC) is a multipotent cell population which arises in the dorsal neural plate/non-neural ectoderm border region during vertebrate embryogenesis. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner.

Neural crest cells