Fig. 6.

Glycocode model: 3-OST-5 and 3-OST-6 regulate distinct cell signaling pathways for ciliogenesis and cilia motility. Schematic of glycocode regulation of cilia length and cilia motility. 3-OST-5 and FGF pathway perturbations have the same downstream molecular and short cilia phenotypes, and display dose-dependent genetic interactions. Therefore, we propose that 3-OST-5 generates a glycocode (blue) on HS chains on proteoglycans (indicated by HSPGs) that modulates interactions of FGF ligands (for example, Fgf8 and Fgf24) and Fgfr1 at the cell surface. It is important to note that the modifications can be on the same HSPG core protein (as shown HSPG for simplicity) or multiple different HSPGs in the same cell. This interaction activates downstream ciliogenic transcription factors including foxj1a and rfx2 for normal length KV cilia. By contrast, 3-OST-6 generates a different glycocode (green) that modulates a distinct pathway regulating kif3b expression, dynein arms and cilia motility.