Using the zebrafish to screen for defects in craniofacial development

Defects in midfacial development, including cleft lip/palate, account for a large number of birth defect each year. In all vertebrates, neural crest cells migrate from the dorsal neural tube to contribute to most of the craniofacial skeleton. In order to better understand the etiology of these defects, we are examining the the gene regulatory networks that regulate normal neural crest and craniofacial development in zebrafish, many of which are causitive in models of facial clefting. To examine this, we have taken multiple approaches in the zebrafish: Morpholino based gene knockdown, ENU mutagenesis, and miRNA expression profiling. These methods have elucidated several genes, genetic loci and miRNAs that are involved in craniofacial development. Specifically, we have identified several transcriptional regulators, including vgl2a and members of the prdm family, as playing roles in specific aspects of craniofacial development. We have further identified several mutants in an ENU mutagenesis screen that have specific defects in pharyngeal skeleton that will be discussed. Lastly, by miRNA profiling in the mouse midface, we have identified miRNAs that play a role in midfacial development. By defining genes, genetic loci, and miRNAs involved in craniofacial development, we will elucidate the gene regulatory networks involved in facial development, which is key to understanding the genetic events leading to human midfacial birth defect syndromes.