During embryonic development individual cells within the embryo must respond appropriately to a multitude of ‘signals’ to yield distinct cell types. Currently, how immature embryonic cells ‘decide’ their fate is not fully understood. Precise control of cell fate ‘decisions’ is encoded in the genome in the form of multifactorial gene regulatory networks. However, the complexities of such networks are not understood at the mechanistic level.

This problem is exemplified in the neural plate border (NPB). The NPB is a discrete, transient region of the early developing embryo. Cells within the NPB region give rise to neural crest and sensory placode cells as well as some neural and epidermal progenitors. Neural crest cells in turn contribute to a wide range of derivatives in the vertebrate body, including elements of the peripheral nervous system, parts of the heart, pigment cells and craniofacial structures. While placode cells contribute to the cranial sensory systems, nose, ears, and lens. Defects in the ontogeny of neural crest and sensory placodes are associated with one-third of all congenital birth defects. Including a number of neurocristopathies such as CHARGE syndrome and Hirschsprungs disease, which present with facial abnormalities, growth deficiency, heart defects and defective enteric nervous system innervation, respectively. Furthermore, a number of cancers are known to arise from neural crest derivatives such as melanoma, neuroblastoma, and glioma.

It is not known how the NPB is endowed with such unique multipotency and, when and how individual NPB cells are directed towards different lineages (i.e., neural crest or placodes). Tackling these questions has proved challenging due to the sparsity and transitory nature of NPB cells. Research in the Williams laboratory combines next-generation single-cell ‘Multiomics’ with innovative developmental biology techniques, to resolve the complex gene regulatory networks underlying cell fate decisions from the emerging NPB, using the chicken embryo as our model system.

Unravelling the intricate gene regulatory networks driving cell fate decisions will help us understand the underlying cause(s) of disease as well as identifying potential targets for therapeutic intervention.