C2CD3 links tooth patterning to evolutionary tooth loss in birds and dental anomalies across vertebrates.

In 24 patients with C2CD3 variants, dental defects affecting tooth number, shape, and timing are linked to disrupted primary cilia function, with nine rare and seven novel variants identified.

• Why it matters: Dental anomalies in ciliopathies remain poorly explained mechanistically, and the study addresses how C2CD3-dependent cilia signaling patterns the jaw and dentition during development.
• What they did: The authors analyzed embryonic mouse and avian models: Ap2Cre;C2cd3 ex4-5 fl/fl mutants and talpid 2 embryos were examined for prenatal dental phenotypes and Shh expression changes.
• The result: In mice, Shh is upregulated in the developing upper jaw with reduced Shh in the lower jaw, while avian mutants show SHH upregulation in both jaws, alongside cartilage defects.