Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation.

Area of Science:

• Developmental biology
• Genetics
• Molecular biology

Background:

• Sox9 is essential for cartilage specification and organogenesis.
• Mechanisms controlling access of transcription factors like Sox9 to cartilage-specific regulatory regions during skeletal development remain unclear.

Purpose of the Study:

• To investigate how chromatin accessibility is dynamically established during chondrogenesis.
• To determine the role of transcription factor Foxc1 in regulating chromatin accessibility and cartilage development in zebrafish.

Main Methods:

• Analysis of chromatin accessibility during neural crest cell differentiation into chondrocytes in zebrafish.
• Investigated transcription factor binding motifs (Sox9 and Fox) in accessible chromatin regions.
• Utilized zebrafish transgenesis assays to functionalize identified regulatory elements.

Main Results:

• Cartilage-associated chromatin accessibility is dynamically established during zebrafish head chondrogenesis.
• Accessible regions are enriched for Sox9 and Fox transcription factor binding motifs.
• Loss of Foxc1 paralogs leads to global decrease in chondrocyte chromatin accessibility and loss of dorsal facial cartilages.
• Foxc1-dependent elements function as enhancers with specific activity in facial cartilages.

Conclusions:

• Foxc1 plays a critical role in promoting facial chondrogenesis by establishing chromatin accessibility.
• This accessibility is essential for the function of cartilage-associated gene enhancers.