An - regulatory axis controls midface morphogenesis in vertebrates.

and are important for palate development across vertebrates. In zebrafish, we found that regulates the expression of We detailed overlapping and expression in mouse orofacial epithelium. In zebrafish, and share expression in periderm, frontonasal ectoderm and oral epithelium. Genetic disruption of and in zebrafish resulted in cleft of the anterior neurocranium. The mutant also developed cleft of the mouth opening. Lineage tracing of cranial neural crest cells revealed that the cleft resulted not from migration defect, but from impaired chondrogenesis. Analysis of aberrant cells within the cleft revealed expression of , and , and these cells were adjacent to and cells. Breeding of mouse ; ; compound mutants suggested genetic interaction, as the triple homozygote and the ; double homozygote were not observed. Further, heterozygosity reduced cleft severity. These studies highlight the complementary analysis of and in mouse and zebrafish, and identify a unique aberrant cell population in zebrafish expressing , and Future work characterizing this cell population will yield additional insight into cleft pathogenesis.