The chick caudo-lateral epiblast acts as a permissive niche for generating neuromesodermal progenitor behaviours

Abstract

Neuromesodermal progenitors (NMps) are a population of bipotent progenitors that maintain competence to generate both spinal cord and paraxial mesoderm throughout the elongation of the posterior body axis. Recent studies have generated populations of NMp-like cells in culture and have been shown to differentiate to both neural and mesodermal cell fates when transplanted into either mouse or chick embryos. Here, we aim to compare the potential of mouse embryonic stem (ES) cell-derived progenitor populations to generate NMp behavior against both undifferentiated and differentiated populations. We define NMp behaviour as the ability of cells to i) contribute to a significant proportion of the anterior-posterior body axis, ii) enter into both posterior neural and somitic compartments and, iii) retain a proportion of the progenitor population within the posterior growth zone. We compare previously identified ES cell-derived NMp-like populations to undifferentiated mouse ES cells and find that they all display similar potentials to generate NMp behaviour in vivo. To assess whether this competence is lost upon further differentiation, we generated anterior and posterior embryonic cell types through the generation of 3D gastruloids and show that NMp competence is lost within the anterior (Brachyury negative) portion of the gastruloid. Taken together, this demonstrates that the chick caudo-lateral epiblast is a highly permissive environment for testing NMp competence and is therefore not suitable as a positive test of neuromesodermal progenitor identity (ie. specification). However, it does act as an appropriate system to test for the loss of NMp potential, and therefore offers insight as a functional test for the regulation of NMp competence in vivo.