Defects in craniofacial development can lead to cleft lip and/or palate – some of the most common types of birth defect. The underlying genetic and environmental causes of such orofacial clefts are complex and remain incompletely understood. Now, Zhongming Zhao, Junichi Iwata and colleagues take a bioinformatics approach to identifying key gene regulatory interactions operating during craniofacial morphogenesis. Using gene expression datasets covering E10.5 to E14.5 of mouse development from the FaceBase initiative, they focus on uncovering dynamic feed-forward loops involving transcription factors, microRNAs and their downstream genes. The authors provide a comprehensive set of potential interactions that may influence craniofacial development at different stages, and conduct some initial validation of some of these networks in cell culture. In particular, they identify the transcription factor Foxm1 and miRNA 340-5p as key regulators of Wnt, FoxO and Hippo signalling during early stages of craniofacial development, and suggest that regulation of the collagen Col1a1 by miR-129-5p may be important throughout the stages analysed. This study provides a valuable resource for researchers interested in the regulatory networks underling craniofacial development, and should spark further investigations into the feed-forward loops identified through these analyses.