Spatial restriction of Dgkk expression within the mandibular prominence shapes the jaw

Endothelin signaling is essential for jaw formation, conferring mandibular identity to neural crest-derived progenitors in the first pharyngeal arch (PA) at midgestation. However, the downstream components of the endothelin pathway that establish the segmental identity and final shape of the mandible have remained unknown.

Here, we identified Diacylglycerol kinase kappa (Dgkk) as a transcriptional target and effector of the endothelin pathway. We demonstrate that Dgkk expression in mice is controlled by a neural crest-specific enhancer that integrates endothelin and BMP signaling to confine expression to the oral, distomedial subdomain of PA1. Moreover, inactivation of Dgkk leads to a disruption of PA1 patterning, resulting in a uniquely misshapen mandible at birth.