The Bush lab has been awarded the prestigious "Sustaining Outstanding Achievement in Research" (SOAR) R35 award from the National Institute of Dental and Craniofacial Research. This award provides longer-term (6-8 years) of support to labs with an outstanding record of research productivity to enable ambitious longer-term projects of extraordinary potential. Our proposal focuses on understanding basic cellular mechanisms of mamallian craniofacial morphogenesis with three main goals: 1) To understand cellular mechanisms of lip and secondary palate formation at cellular resolution, and how these go wrong in cleft lip and palate 2) To understand how distinct mesenchymal populations in the craniofacial complex are segregated and lead to distinct craniofacial tissue structures, and the signaling pathways that control this process. 3) To use novel CRISPR/Cas9 genome engineering approaches to generate and study novel mouse models of craniofacial congenital disease.