SLS/WMS Development Biology and Stem Cell Seminar Series Sponsored by Nikon and The Physiological Society

Abstract: The neural crest (NC) is a transient population of stem cell-like cells which generate numerous derivatives in the vertebrate embryo. These include neurons and glia of the peripheral and enteric nervous system and mesenchymal craniofacial elements including cartilage and bone, and all skin pigments cells. Neural crest progenitors are thought to originate from the neural plate border territory which they share with cranial placode anlagen. Exactly when and how cells within the neural plate border segregate into different lineages remains elusive. Precise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and dynamic molecular interactions. We recently reconstructed comprehensive GRNs governing early NC development in the chick embryo, detailing transcriptional as well as epigenomic dynamics at population and single-cell levels. Using genome/epigenome engineering in vivo, we validated multiple regulatory layers governing NC ontogeny, including NC-specific enhancers and novel trans-factors. Furthermore, identification and dissection of divergent upstream combinatorial regulatory codes has afforded new insights into opposing regulatory circuits that define neural and mesenchymal NC fates during early NC ontogeny. In addition, we find shared regulatory programmes driving NC lineage progression from the neural plate border. Finally, using single-cell RNA-seq we find a subpopulation of early NC cells shares a transcriptional signature with neurula stage ectoderm cells and developmental trajectory analysis shows neural plate border lineages only begin to segregate at early neurulation.