Ciliogenesis

Ciliogenesis is defined as the building of the cell's antenna (primary cilia) or extracellular fluid mediation mechanism (motile cilium). It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organelles of cells and are involved in numerous activities such as cell signaling, processing developmental signals, and directing the flow of fluids such as mucus over and around cells. Due to the importance of these cell processes, defects in ciliogenesis can lead to numerous human diseases related to non-functioning cilia. Ciliogenesis may also play a role in the development of left/right handedness in humans. Ciliogenesis is defined as the building of the cell's antenna (primary cilia) or extracellular fluid mediation mechanism (motile cilium). It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organelles of cells and are involved in numerous activities such as cell signaling, processing developmental signals, and directing the flow of fluids such as mucus over and around cells. Due to the importance of these cell processes, defects in ciliogenesis can lead to numerous human diseases related to non-functioning cilia. Ciliogenesis may also play a role in the development of left/right handedness in humans. Ciliogenesis occurs through an ordered set of steps. First, the basal bodies from centrioles must migrate to the surface of the cell and attach to the cortex. Along the way, the basal bodies attach to membrane vesicles and the basal body/membrane vesicle complex fuses with the plasma membrane of the cell. Fusion with the plasma membrane is likely what forms the membrane of the cilia. The alignment of the forming cilia is determined by the original positioning and orientation of the basal bodies. Once the alignment is determined, axonemal microtubules extend from the basal body and go beneath the developing ciliary membrane, forming the cilia. Proteins must be synthesized in the cytoplasm of the cell and cannot be synthesized within cilia. For the cilium to elongate, proteins must be selectively imported from the cytoplasm into the cilium and transported to the tip of the cilium by intraflagellar transport (IFT). Once the cilium is completely formed, it continues to incorporate new tubulin at the tip of the cilia. However, the cilium does not elongate further, because older tubulin is simultaneously degraded. This requires an active mechanism that maintains ciliary length. Impairments in these mechanisms can affect the motility of the cell and cell signaling between cells. Most cilia (also known as flagella) form as a separate compartment in the cell and the process is named Compartmentalized ciliogenesis. However, the flagellum, a particular type of cilium found in the sperm is formed in a unique way, which is named Cytosolic ciliogenesis (also known as Cytoplasmic ciliogenesis), since, in this type of ciliogenesis, the cilium axoneme is formed in the cytoplasm or get exposed to the cytoplasm. Ciliary defects can lead to a broad range of human diseases known as ciliopathies that are caused by mutations in ciliary proteins. Some common ciliopathies include primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration. Some research has shown that mutations in ciliary proteins can lead to other developmental and adult phenotypes such as nephronophthisis, Bardet-Biedl syndrome, Alström syndrome, and Meckel-Gruber syndrome.