9b. Below is a list of defects/diseases resulting from abnormal cilia assembly or function. For each, indicate which of the cellular processes from the first part of this question is/are associated with each of the defects/diseases, and provide a brief explanation of the connection between cilia assembly or function and the mechanisms/symptoms of the disease. To put that another way, what is the mechanistic connection between cilia assembly or function and the specific class of diseases?
- Cystic diseases: with cilia involved in SENSORY organs. In Polycystic kidney disease, primary cilia are NON-motile, possibly due to a bending of the cilia causing opening of Ca channels and then signaling cascade leading to cell proliferation and cysts in liver.
- Retinitis pigmentosa: with cilia involved in SENSORY organs, and possibly involved with IFT. Mutations in kinesin KIF3A leads to accumulation of opsin and membranes at the base of the cilium causing retinal degeneration. Defect in rhodopsin blocks transport to the outer segment. Not clear if the primary cause for retinal degeneration is intraflagellar transport.
- Anosmia: cilia involved in SENSORY organs. Disease causes inability to smell, due to defective non-motile 9+0 sensory cilia present on olfactory neurons, Also a symptom of Bardt-Biedl Syndrome
- Cancer: with cilia involved in CELL DIVISION. Mutations causing loss of cilia signaling ability can causing cell proliferation and loss of cell cycle control.
- Situs inversus: with cilia and cell motility. In this case, there is mutation that interfere with normal assembly of nodal cilia. Primary cilia on node are immotile. Usually these are motile (disobey the 9+0 immotile rule). Nodal gene expression is critical for formation of either R or L side.
- Impaired wound healing: with cilia cell signaling and movement. Fibroblast primary cilia play a role in signaling to monitor directional movement of fibroblasts during wound healing
- Diabetes: with cilia sensory structure/function. It is a symptom of Bardt-Biedl Syndrome
- Skeletal patterning: with cilia involved in sensory organs. Plays a role in chemosensation and mechano sensation.