Cdonor

Cdon is a vertebrate cell-surface receptor encoded by the CDON gene. The name stands for cell adhesion molecule-related/down-regulated by oncogenes, and the protein is a member of the immunoglobulin superfamily of cell-surface adhesion molecules. Cdon functions as a co-receptor for Hedgehog signaling, helping cells respond to Hedgehog ligands during embryonic development. In mammals, Cdon belongs to a small family that also includes Boc and Gas1, which can act in overlapping or compensatory fashion to modulate Hedgehog pathway activity.

Structure and expression: Cdon is a single-pass transmembrane glycoprotein with extracellular domains that mediate ligand binding. It is expressed in developing embryos, including neural tube and limb buds, where Hedgehog signaling patterns cell fate.

Function and mechanism: By forming part of the Hedgehog receptor complex, Cdon modulates the activity of the Patched1 receptor and the Gli transcription factors, influencing gradient interpretation and downstream gene expression. Its activity contributes to proper neural tube patterning and skeletal development in model organisms.

Genetics and disease: Mouse studies show that loss of Cdon leads to developmental defects consistent with reduced Hedgehog signaling. In humans, rare CDON variants have been found in individuals with neural tube defects or holoprosencephaly-like craniofacial anomalies, particularly when combined with disruptions in other Hedgehog pathway components. The clinical significance is still being studied.

Clinical and research relevance: Understanding Cdon's role helps elucidate Hedgehog signaling in development and disease and may inform studies of congenital malformations and cancer, where adhesion molecules and Sonic Hedgehog signaling intersect.