Abstract
OBJECTIVE: Craniofacial growth and development are more than a scientific curiosity; it is of tremendous interest to clinicians. Insights into the genetic etiology of cleft lip and palate development are essential for improving diagnosis and treatment planning. The purpose of this systematic review was to utilize a zebrafish model to highlight the role of the IRF6 gene in cleft lip and palate development in humans. DATA: This review adhered to the guidelines outlined in the PRISMA statement. Nine studies were included in the analysis. SOURCES: This study used major scientific databases such as MEDLINE, EMBASE, Web of Science, and the Zebrafish Information Network and yielded 1275 articles. Two reviewers performed the screening using COVIDENCE™ independently, and a third reviewer resolved any conflicts. STUDY SELECTION: After applying the inclusion and exclusion criteria and screening, nine studies were included in the analysis. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE's) risk-of-bias tool was used to assess the quality of the included studies. RESULTS: The main outcome supports the role of the IRF6 gene in zebrafish periderm development and embryogenesis, and IRF6 variations result in cleft lip and palate development. The overall SYRCLE risk of bias was low-medium. CONCLUSION: In conclusion, this review indicated the critical role of the IRF6 gene and its downstream genes (GRHL3, KLF17, and ESRP1/2) in the development of cleft lip and palate in zebrafish models. Genetic mutation zebrafish models provide a high level of insights into zebrafish craniofacial development. CLINICAL RELEVANCE: this review provides a productive avenue for understanding the powerful and conserved zebrafish model for investigating the pathogenesis of human cleft lip and palate.