Figure 8. Hypothetical schema of the HS-dependent TGF-β₂ signaling on the cell surface of neural crest cells.

(A) HS has an affinity for TGF-β₂, which enhances the ligand presentation to the TGF-β receptors. Subsequently, transduction of the signal to the nucleus occurs via phosphorylation of the Smads. (B) For the HS defect, there is deterioration of the efficiency of the interaction between TGF-β₂ and the receptors, which leads to a disturbance of the Smads phosphorylation. The loss of phosphorylated Smads then inhibits the expression of Foxc1 and Pitx2.