UNASSIGNED: 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.
UNASSIGNED: This review adhered to the guidelines outlined in the PRISMA statement. Nine studies were included in the analysis.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: this review provides a productive avenue for understanding the powerful and conserved zebrafish model for investigating the pathogenesis of human cleft lip and palate.

Deconjugation of ubiquitin and/or ubiqutin-like modified substrates is essential to maintain a sufficient free ubiquitin within the cell. Deubiquitinases (DUBs) play a key role in the process. Besides, DUBs also play several important regulatory roles in cellular processes. However, our knowledge of their developmental roles are limited. The report here aims to study their potential roles in craniofacial development. Based on the previous genome-wide study in 2009, we selected 36 DUBs to perform the morpholino (MO) knockdown in this study, followed by the Alcian blue cartilage staining at 5 days post-fertilization (dpf) larvae to investigate the facial development. Results classified the tested DUBs into three groups, in which 28% showed unchanged phenotype (Class 1); 22% showed mild changes on the branchial arches (Class 2A); 31% had malformation on branchial arches and ethmoid plate (Class 2B); and 19% had severe changes in most of the facial structures (Class 3). Lastly, we used uchl3 morphant as an example to show that our screening data could be useful for further functional studies. To summarize, we identified new craniofacial developmental role of 26 DUBs in the zebrafish.

Craniofacial development relies on coordinated tissue interactions that allow for patterning and growth of the face. We know a priori that the Wingless, fibroblast growth factor, Hedgehog and transforming growth factor-beta growth factor signaling pathways are required for the development of the face, but how they contribute to the shape of the face is largely untested. Here, we test how each signaling pathway contributes to the overall morphology of the zebrafish anterior neurocranium. We tested the contribution of each signaling pathway to the development of the ethmoid plate during three distinct time periods: the time of neural crest migration [10 hour post fertilization (hpf)]; once the neural crest is resident in the face (20 hpf); and finally at the time at which the cartilaginous condensations are being initiated (48 hpf). Using geometric morphometric analysis, we conclude that each signaling pathway contributes to the shape, size and morphology of the ethmoid plate in a dose-, and time-dependent fashion.