The hedgehog co-receptors cdon and boc function redundantly to regulate zebrafish craniofacial development.

Area of Science:

• Developmental Biology
• Genetics
• Zebrafish Models

Background:

• Craniofacial development is intricate, involving skeletal, muscular, and tendon formation.
• Defects lead to hereditary disorders; hedgehog signaling dysregulation is linked to orofacial clefting and holoprosencephaly.
• Cdon and boc, hedgehog signaling co-receptors, are implicated in microform holoprosencephaly, but their specific craniofacial roles in zebrafish are uncharacterized.

Purpose of the Study:

• To characterize craniofacial phenotypes associated with cdon and boc in zebrafish.
• To elucidate the redundant roles of cdon and boc in craniofacial development.
• To investigate the molecular mechanisms underlying cdon and boc function in craniofacial development.

Main Methods:

• Zebrafish model system utilized for phenotypic analysis.
• RNA sequencing (RNA-seq) to assess gene expression changes.
• Hybridization chain reaction (HCR) in situ hybridization for spatial gene expression analysis.

Main Results:

• Cdon and boc act redundantly to support craniofacial cartilage, tendon, and muscle development in zebrafish.
• Mutations in cdon and boc lead to misregulation of chondrogenesis gene expression.
• Key genes affected include Indian hedgehog ligand, thrombospondin genes, and FOX transcription factors.

Conclusions:

• Cdon and boc function together to modulate hedgehog signaling in the head.
• These findings establish a foundation for using zebrafish to study cdon and boc in craniofacial hereditary disorders.
• The study highlights the importance of cdon and boc in preventing craniofacial skeletal defects like holoprosencephaly.