Figure 4.

The physiological structure and functioning of the Primary Cilium are prerequisites for proper Shh pathway which is responsible for an adequate skeletal development, tissue patterning and thus an ordered cartilage and bone growth. Particularly, the Intraflagellar Transport (IFT) associated proteins are of high importance in this respect. Without Shh signal gli proteins (grey circles) are activated (yellow flashes) to their repressor form (red pentagons) by the inhibition of Smo (purple wavy line) via the Ptc receptor (pink wavy line). In the presence of Shh (yellow hexagon) Ptc is blocked and Smo is released to the cilium, where gli proteins are activated to their transcriptional activator forms (orange triangles). The anterograde and retrograde transport function along the Axoneme via IFT motor proteins (Kinesin and Dynein) enables the translocation of the Gli transcription factors to the nucleus. Thus, the transcription of important genes during skeletal development is regulated. Disorders within this complex cascade lead to skeletal abnormalities. Image modified from Singla & Reiter (2006) [5].