The fusome is a membranous structure found in the developing germ cell cysts of many insect orders.Telfer, W. H. 1975. Development and physiology of the oocyte-nurse cell syncytium. Advances in insect physiology 11:223-319. DOI: 10.1016/S0065-2806(08)60164-2Snapp, E. L., T. Iida, D. Frescas, J. Lippincott-Schwartz, and M. A. Lilly. (2004). The fusome mediates intercellular endoplasmic reticulum connectivity in ''Drosophila'' ovarian cysts. Mol Biol Cell 15: 4512-4521. doi/10.1091/mbc.E04 – 06 – 0475.Greenbaum, M. P., T. Iwarmori, G. M. Buchold, and M. M. Matzuk. (2011). Germ Cell Intercellular Bridges. Cold Spring Harb Perspect Biol 3:a005850 doi: 10.1101/cshperspect.a005850 Initial description of the fusome occurred in the 19th century and since then the fusome has been extensively studied in ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

'' male and female

germline In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...

development. This structure has roles in maintaining germline cysts, coordinating the number of

mitotic Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the t ...

divisions prior to

meiosis Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...

, and

oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...

determination by serving as a structure for intercellular communication.de Cuevas, M., J. K. Lee, A. C. Spradling. (1996) α-spectrin is required for germline cell division and differentiation in the ''Drosophila'' ovary. Development 122: 3959-3968.Lilly, M. A., M. de Cuevas, and A. C. Spradling. (2000). Cyclin A associates with the fusome during germline cyst formation in the Drosophila ovary. Developmental Biology 218: 53-63. doi:10.1006/dbio.1999.9570

Structure

In ''D. melanogaster'', germline cysts form from four mitotic divisions with incomplete

cytokinesis Cytokinesis () is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division ...

that originated from one germline stem cell.Spradling, A. C. (1993). Developmental genetics of oogenesis. In The Development of Drosophila, M. Bate and A. Martinez-Arias, eds. (Cold Spring Harbor, New York: Cold Spring Harbor Press), pp. 1–70. Fuller, M.T. (1993). Spermatogenesis. In The Development of Drosophila, M. Bate and A. Martinez-Arias, eds. (Cold Spring Harbor, New York: Cold Spring Harbor Press), pp. 71–147. Incomplete cytokinesis results in intercellular bridges connecting every cell in the cyst, called ring canals³. The four mitotic divisions result in cysts of 16 cells connected by 15 ring canals. The fusome is composed of membrane vesicles and originates from

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. Fusome material is inside ring canals and can range in size from 1 to 10 um, depending on the stage of development. 1.1 Fusome Development The spectrosome is a round structure in germline stem cells that develops into the fusome in cyst cells.Lin, H. and Spradling, A. C. (1995). Fusome asymmetry and oocyte determination in ''Drosophila''. ''Dev. Genet.'' 16: 6-12. Fusome divides asymmetrically into daughter cells in females by attaching to one

spindle pole In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process ...

during meiosis, resulting in one cell receiving all fusome material.de Cuevas, M. and A. C. Spradling. (1998). Morphogenesis of the ''Drosophila'' fusome and its implicaitons for oocyte specification. Development 125: 2781-2789.Roth, S. and J. A. Lynch. (2009). Symmetry breaking during ''Drosophila'' oogenesis. Cold Spring Harb Perspect Biol 1:a001891 doi: 10.1101/cshperspect.a001891 Fusome is generated ''de novo'' in the ring canal connecting the two cells. The two fusome parts then fuse together to connect the cells. Asymmetric fusome partitioning and new formation followed by fusion occurs at each mitotic division. In

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...

, the fusome partitioning is symmetric and the fusome is still present during the meiotic divisions. 1.2 Fusome components Many proteins and organelles associate with the fusome throughout germ cell development.

Cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

components, such as alpha and beta

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma mem ...

s, hu-li tai shao (hts), and

ankyrin Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...

were the first proteins identified in the fusome.Lin, H., L. Yue, and A. C. Spradling. (1994). The ''Drosophila'' fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation. Development 120: 947-956.

Centrosome In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progre ...

s travel along the fusome and the fusome is involved in

microtubule 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 nanometer, nm and have an inner diameter bet ...

organization.Grieder, N., M. de Cuevas, and A. C. Spradling. (2000). The fusome organizes the microtubule network during oocyte differentiation in ''Drosophila''. Development 127: 4253-4264. The interactions between the fusome and microtubules result in cyst polarity in

oogenesis Oogenesis () or ovogenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated before birth during embryonic devel ...

. Associations between the fusome and microtubules change throughout the cell cycle.

Mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

associates with the fusome and travel through ring canals to the oocyte. Microtubules travel through ring canals and form the tracks for transport of materials between cells.

Function

There are numerous functions of the fusome as a structure necessary for cell-cell communication in developing germ cell cysts. The fusome connects cells, allowing for transport of proteins and RNAs between cells and synchronous activities. Mutations in essential fusome components can result in

infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...

. 2.1 Role in cell cycle synchrony Developing cells in germline cysts undergo mitotic divisions synchronously and in males all cells in a cyst also undergo meiosis synchronously. The fusome is a track where an event can happen and then feedback mechanisms quickly communicate to each cell to ensure a specific outcome occurs simultaneously in every cell. Cells in a cyst fail to divide synchronously if the fusome is disrupted. The rosette formation of germline cyst cells allows cells to be in the closest configuration for communication. Throughout the cell cycle, different

cyclin Cyclins are proteins that control the progression of a cell through the cell cycle by activating cyclin-dependent kinases (CDK). Etymology Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urch ...

s associate with the fusome to induce synchronous cell divisions.

Cyclin A Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cel ...

and

Cyclin E Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27 ...

localize to the fusome in female germline cysts and are required for the correct number of mitotic divisions to occur.Ohlmeyer, J. T. and T. Schupbach. (2003). Encore facilitates SCF-Ubiquitin-proteosome-dependent proteolysis during ''Drosophila'' oogenesis. Development 130: 6339-6349. doi:10.1242/dev.00855 Abnormal

levels result in too few or too many divisions.

at the fusome is phosphorylated for degradation by the

SCF complex Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has impo ...

and if not degraded, an extra division occurs. The fusome may be the degradation site for other cell cycle proteins. Myt1 kinase inhibits CycA/Cdk1 in males during G2.Varadarajan, R., J. Ayeni, Z. Jin, E. Homola, S. D. Campbell. (2016).Myt1 inhibition of Cyclin A/Cdk1 is essential for fusome integrity and premeiotic centriole engagement in ''Drosophila'' spermatocytes. MBoC 27: 2051-2063. doi.org/10.1091/mbc.E16-02-0104 Without Myt1 regulation, fusome and

centrosome In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progre ...

behavior is abnormal, resulting in cells with irregular spindles. 2.2 Differences in male vs female fusomes In females, the fusome plays a role in cell fate and differentiation. Asymmetric fusome distribution and

centriole In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers ( Pinophyta), flowering plants ( angiosperms) and most fungi, an ...

orientation determines which cell in the developing female germline cyst becomes the

. One of the two cells from the first division within the cyst becomes the

and contains the most fusome material. The fusome degrades after the 16-cell cyst forms. In females, the connections are the channels through which

nurse cell In general biology or reproductive physiology, a nurse cell is a cell which provides food, helps other cells and provides stability to neighboring cells. The term nurse cell is used in several unrelated ways in different scientific fields. Human p ...

s send proteins and RNAs to the oocyte along polarized

s. In males, the fusome is necessary for ensuring quality control in individual cysts.

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

in one cell leads to all cells in a cyst dying by communication through the fusome, either by disseminating a death signal or additive DNA damage inducing

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

.Lu, K. L. and Y. M. Yamashita. (2017). Germ cell connectivity enhances cell death in response to DNA damage in the ''Drosophila'' testis. eLife 6:e27960. doi.org/10.7554/eLife.27960 This ensures mature

sperm cells A spermatozoon (; also spelled spermatozoön; : spermatozoa; ) is a motile sperm cell produced by male animals relying on internal fertilization. A spermatozoon is a moving form of the haploid cell that is the male gamete that joins with an ov ...

have intact

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

s before fertilizing an egg. In addition, the fusome connections ensure

haploid Ploidy () is the number of complete sets of chromosomes in a cell (biology), cell, and hence the number of possible alleles for Autosome, autosomal and Pseudoautosomal region, pseudoautosomal genes. Here ''sets of chromosomes'' refers to the num ...

spermatid The spermatid is the haploid male gametid that results from division of secondary spermatocytes. As a result of meiosis, each spermatid contains only half of the genetic material present in the original primary spermatocyte. Spermatids are co ...

s have proteins and RNA made by the other

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

for “gamete equivalency”.

Similar structures in other animals

Fusomes were previously thought to be specific to insect

gametogenesis Gametogenesis is a biological process by which diploid or haploid precursor cells undergo cell division and differentiation to form mature haploid gametes. Depending on the biological life cycle of the organism, gametogenesis occurs by meiotic d ...

. Fusome-like structures have been identified in ''

Xenopus laevis The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black ...

electron microscopy An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...

and

immunostaining In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by ...

for fusome components such as

and hts.Kloc, M., S. Bilinski, M. T. Dougherty, E. M. Brey, and L. D. Etkin. (2004). Formation, architecture and polarity of female germline cyst in ''Xenopus''. Dev Biol 266: 43-61. doi:10.1016/j.ydbio.2003.10.002

Intercellular bridge Intercellular communication (ICC) refers to the various ways and structures that biological cell (biology), cells use to communicate with each other directly or through their environment. Often the environment has been thought of as the extracellu ...

s also connect developing germ cells in

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s, contributing to cell cycle synchrony and gamete quality control by sharing substances between cells. Future studies are required to elucidate all of the functions that arise from cell-cell communication through

intercellular bridge Intercellular communication (ICC) refers to the various ways and structures that biological cell (biology), cells use to communicate with each other directly or through their environment. Often the environment has been thought of as the extracellu ...

s. In addition, a future area of research is to determine why some organisms lack fusomes. Do these organisms have another structure that carries out the role of the fusome or are these roles not necessary in germline cyst development of these other organisms?

References

^PG Wilson Cell Biol Int. 2005 May;29(5):360-9. Centrosome inheritance in the male germ line of Drosophila requires hu-li tai-shao function.

External links

*Huynh JR. (2006) Fusome as a Cell-Cell Communication Channel of ''Drosophila'' Ovarian Cyst. In: Cell-Cell Channels. Springer, New York, NYhttps://www.ncbi.nlm.nih.gov/books/NBK6300/ *http://www.oxfordreference.com/view/10.1093/acref/9780195307610.001.0001/acref-9780195307610-e-2383?rskey=LqAWUj&result=2381 *Lighthouse, D. V., M. Buszczak, and A. C. Spradling. (2008). New components of the ''Drosophila'' fusome suggest it plays novel roles in signaling and transport. Dev Biol 317: 59–71. doi:10.1016/j.ydbio.2008.02.009 *de Cuevas, M., M. A. Lilly, and A. C. Spradling. (1997). Germline cyst formation in ''Drosophila''. Annu. Rev. Genet. 31: 405–428. DOI: 10.1146/annurev.genet.31.1.405 *Yamashita, Y. M., H. Yuan, J. Cheng, and A. J. Hunt. (2010). Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol 2:a001313 doi: 10.1101/cshperspect.a001313 *Rieger R. Michaelis A., Green M. M. (1976). Glossary of genetics and cytogenetics: Classical and molecular. Heidelberg - New York: Springer-Verlag. . *King R. C., Stransfield W. D. (1998): Dictionary of genetics. Oxford University Press, New York, Oxford, ; {{ISBN, 0-19-509442-5. Cell biology

Structure

Function

Similar structures in other animals

See also

References

External links