Spatio-temporal structure of cell fate decisions in murine neural crest. Spatio-temporal structure of cell fate decisions in murine neural crest

Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single cell analysis, we show that mouse trunk neural crest cells become biased toward neuronal lineages when they delaminate from the neural tube, whereas cranial neural crest cells acquire ectomesenchyme potential dependent on activation of the transcription factor Twist1. The choices that neural crest cells make to become sensory, glial, autonomic, or mesenchymal cells can be formalized as a series of sequential binary decisions. Each branch of the decision tree involves initial co-activation of bipotential properties followed by gradual shifts towards commitment. Competing fate programs are co-activated before cells acquire fate-specific phenotypic traits. Determination of a specific fate is achieved by increased synchronization of relevant programs and concurrent repression of competing fate programs. Overall design: Analysis of neural crest developmental landscape using single-cell expression profiling across developmental stages and rostro-caudal axis