Zebrafish models of orofacial clefts

Area of Science:

• Developmental Biology
• Genetics
• Model Organism Research

Background:

• Orofacial cleft (OFC) is a common congenital birth defect.
• Understanding the genetic basis of OFC is critical for diagnosis and treatment.
• Zebrafish offer unique advantages for studying gene function in craniofacial development.

Purpose of the Study:

• To summarize the utility of zebrafish in studying genes associated with orofacial cleft.
• To review different zebrafish-based approaches for investigating OFC-related genes.
• To highlight the application of zebrafish in understanding craniofacial morphogenesis.

Main Methods:

• Gene expression inhibition using antisense morpholino oligonucleotides.
• CRISPR/Cas9 gene editing for targeted mutagenesis.
• In vivo functional assays for patient-derived gene variants.
• Analysis of enhancer activity and tissue specificity using reporter assays.

Main Results:

• Zebrafish orthologs effectively model the function of OFC-associated genes.
• CRISPR/Cas9 has become a preferred method for gene manipulation.
• In vivo zebrafish assays provide valuable validation for in silico predictions of variant severity.
• Zebrafish enable testing of regulatory elements linked to OFC risk.

Conclusions:

• Zebrafish are a powerful model for dissecting the genetic and regulatory mechanisms underlying orofacial cleft.
• The diverse experimental approaches in zebrafish facilitate comprehensive investigation of OFC pathogenesis.
• This model system aids in understanding both syndromic and non-syndromic forms of OFC.