With birth defects impacting ~3% of all infants born and ~75% of these affecting the head and oral cavity, a comprehensive understanding of the genetic and molecular mechanisms at play is essential. One such mechanism, essential for proper craniofacial development, is finely tuned tissue:tissue communication. However, how these signals are properly generated, augmented, and then interpreted—between tissues—is not well understood. Our lab’s research utilizes a combination of sophisticated animal models, genetics, and modern molecular biology based next generation sequencing approaches to unravel these complex interconnected networks. For example, we are investigating key proteins that are found, and regulate, these various ‘nodes’ of tissue:tissue communication during craniofacial development. In turn, we anticipate the principles discovered will ultimately guide how we understand, predict, and mitigate mechanisms associated with craniofacial birth defects.