Ciliogenesis is defined as the building of the cell's

antenna Antenna ( antennas or antennae) may refer to: Science and engineering * Antenna (radio), also known as an aerial, a transducer designed to transmit or receive electromagnetic (e.g., TV or radio) waves * Antennae Galaxies, the name of two collid ...

(

primary cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

) or extracellular fluid mediation mechanism (

motile cilium The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

). It includes the assembly and disassembly of the cilia during the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

. Cilia are important

organelles In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

of cells and are involved in numerous activities such as

cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

, 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 human biology, handedness is an individual's preferential use of one hand, known as the dominant hand, due to it being stronger, faster or more Fine motor skill, dextrous. The other hand, comparatively often the weaker, less dextrous or sim ...

in humans.

Cilia formation

Ciliogenesis occurs through an ordered set of steps.Sorokin, S. Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. ''J. Cell Biol.'' 15, 363–377 (1962). First, the

basal bodies A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor W ...

from centrioles must migrate to the surface of the cell and attach to the

cortex Cortex or cortical may refer to: Biology * Cortex (anatomy), the outermost layer of an organ ** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain'' *** Motor cortex, the regions of the cerebral cortex i ...

. Along the way, the basal bodies attach to membrane

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

and the basal body/membrane vesicle complex fuses with the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

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 Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

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 Intraflagellar transport (IFT) is a bidirectional motility along axoneme microtubules that is essential for the formation (ciliogenesis) and maintenance of most eukaryotic cilia and flagella. It is thought to be required to build all cilia that ass ...

(IFT). Once the cilium is completely formed, it continues to incorporate new

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

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.

Ciliogenesis types

Most cilia (also known as flagella) form as a separate compartment in the cell and the process is named

compartmentalized ciliogenesis Compartmentalized ciliogenesis is the most common type of ciliogenesis where the cilium axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and ...

. However, the flagellum, a particular type of cilium found in the sperm is formed in a unique way, which is named

cytosolic ciliogenesis Cytosolic ciliogenesis, otherwise cytoplasmic ciliogenesis, is a type of ciliogenesis where the cilium axoneme is formed in the cytoplasm or becomes exposed to the cytoplasm. Cytosolic ciliogenesis is divided into three types: Primary cytosolic ci ...

(also known as cytoplasmic ciliogenesis), since, in this type of ciliogenesis, the

cilium The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axo ...

is formed in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

or get exposed to the cytoplasm.

Ciliopathies

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 Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of ...

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...

, polycystic liver and

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...

, and some forms of retinal degeneration. Some research has shown that mutations in ciliary proteins can lead to other developmental and adult

phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

such as

nephronophthisis Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause o ...

Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in so ...

Alström syndrome Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dystr ...

, and

Meckel–Gruber syndrome Meckel-Gruber syndrome is a rare, lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (postaxial), hepatic developmental defects, and pulmonary ...

Regulation

Different cells use their cilia for different purposes, such as sensory signaling or the movement of fluid. For this reason, when cilia form and how long they are differ from cell to cell. The processes controlling ciliary formation, degradation, and length must all be regulated in some way to ensure that each cell is able to perform its necessary tasks.

Formation and removal

As the cell containing the cilium goes through the cell cycle, ciliogenesis must be regulated. Cilia usually form during the G1 of the cell cycle and disassemble during

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

. It is not known why the cilia assemble and then disassemble, but it is believed that the presence of cilia may interfere with mitosis and, therefore, are removed before mitosis occurs. Cells that have recently divided and are in the G0 stage of the cell cycle do not have cilia. During G1, the mother centriole attaches at the cell cortex and forms the cilium. During

S-phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...

, the mother centrioles and daughter centrioles (new centrioles) duplicate and new daughter centrioles are formed. Before mitosis can occur in most cells, the cilium is resorbed back into the cell. After the original cell divides into its two new cells, the cilia reform within the cells after the new cells enter G1.

Length

Each type of cell has a specific optimal length for its cilia. Therefore, the length of the cilia must be regulated to ensure optimal function of the cell. Some of the same processes that are used to control to formation and removal of cilia (such as IFT) are thought to be used in the regulation of cilia length. The regulation of ciliary length is very important because it affects how the cell is able to use its cilia to move fluid over its surface or conduct cellular signaling. Different ciliopathies can be caused by defects in ciliary length. For instance, proteins that have been shown to cause Meckel–Gruber syndrome affect ciliary length control.Tammachote, R. et al. Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3. ''Hum. Mol. Genet''. 18, 3311–3323 (2009). However, the mechanisms that affect ciliary length control are not understood very well. Until they are, it will be difficult to determine how defects in ciliary length may related to ciliopathic diseases and syndromes.

References

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