A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest development

The process of cell fate commitment requires sequential changes in the gene expression profiles of embryonic progenitors. This is exemplified in the development of the neural crest, a migratory stem cell population derived from the ectoderm of vertebrate embryos. Neural crest formation involves a series of regulatory changes, in which cells adopt distinct transcriptional states in a stepwise manner. The mechanisms underpinning these shifts in cell identity are still poorly understood. Here we employ enhancer analysis to identify a genetic sub-circuit that controls developmental transitions in neural crest development. This sub-circuit links Wnt target genes in an incoherent forward loop that controls the sequential activation of genes in the neural crest lineage. By examining the cis-regulatory apparatus of Wnt effector gene AXUD1, we found that multipotency factor SP5 directly promotes neural plate border identity, while inhibiting premature specification by interacting with tissue specific enhancers.