The establishment and maintenance of discrete domains of gene expression are critical for early embryonic development. In vertebrates, embryonic patterning is mediated by the combinatorial action of signaling systems and transcription factors. Cooperation between inductive signals is essential for the establishment of the progenitor cell populations that will give rise to distinct tissues and organs. For example, Wnts and BMPs are both required for the formation of the neural crest, a migratory, multipotent cell population that gives rise to important structures like the craniofacial skeleton and the peripheral nervous system. These signals converge at the neural plate border, the embryonic region where neural crest cells will form, to activate the genes that endow these cells with their unique properties. Neural crest formation is controlled by a gene regulatory network (GRN) composed of dozens of genes expressed in a specific spatial domain within the neural plate border. However, the cis-regulatory principles that allow for the emergence of these discrete patterns of gene expression remain poorly understood. To address this, I examined the regulation of GRN components in avian embryos to identify and dissect genomic elements that are regulated by signaling systems. I focused on signaling-responsive enhancers that control the expression of MSX1 and ZFHX4, which are genes important for the formation of the neural plate border and the neural crest, respectively. I employed these genes and their respective regulatory elements as a model to elucidate the cis-regulatory principles that allow enhancers to interpret multiple signaling inputs and produce specific patterns of gene expression.