Ezh2 is required for neural crest-derived cartilage and bone formation

Area of Science:

• Developmental Biology
• Epigenetics
• Evolutionary Biology

Background:

• Craniofacial skeletal elements, particularly the jaw, are vital for vertebrate evolution.
• Cranial neural crest cells form most facial bones and cartilage during embryonic development.
• Hox genes typically suppress osteochondrogenesis in posterior neural crest cells, but the mechanism is unclear.

Purpose of the Study:

• To elucidate the epigenetic mechanisms controlling Hox gene expression and osteochondrogenic competence in neural crest cells.
• To investigate the role of Ezh2 (enhancer of zeste homolog 2) in regulating craniofacial skeletal development.

Main Methods:

• Conditional inactivation of the Ezh2 gene in mice.
• Analysis of neural crest cell localization, neural development, cell cycle, and survival.
• Assessment of Hox gene expression patterns.
• Evaluation of craniofacial bone and cartilage formation in knockout mice.

Main Results:

• Conditional Ezh2 inactivation did not affect neural crest cell migration, neural development, cell cycle, or survival.
• Loss of Ezh2 caused significant derepression of Hox genes in neural crest cells.
• Craniofacial bone and cartilage formation were completely abolished in Ezh2 conditional knockout mice.

Conclusions:

• Epigenetic regulation by Ezh2 is essential for suppressing Hox genes and enabling osteochondrogenic differentiation in cranial neural crest cells.
• The study highlights the critical dependence of craniofacial skeleton formation in higher vertebrates on epigenetic control mechanisms that maintain osteochondrogenic competence.