2013 Group 4 Project
- 1 Spindle Apparatus
- 1.1 Introduction
- 1.2 Historical Research
- 1.3 Structure
- 1.4 Function
- 1.5 Mechanism of Formation
- 1.6 Current research
- 1.7 Complications
- 1.8 Glossary
- 1.9 Images
- 1.10 Useful Links
- 1.11 References
Cell division is the process through which parent cells divide to create new daughter cells. There are two types of cell division: mitosis and meiosis. Spindles are microtubules which attaches to the chromosomes during cell division, to segregate the chromosomes of daughter cells.  The spindle apparatus plays a vital role in chromosome alignment, chromosome segregation and bipolarity, all of which are necessary for correct chromosomal segregation in cell division.   
There are three main types of microtubules involved in mitotic spindles: astral microtubules, kinetochore microtubules, and polar microtubules. During metaphase, the kinetochore microtubules attach to the chromosomes, while the astral microtubules are involved in anchoring the polar ends in position.   The structure of the spindle apparatus is mainly formed by the polar microtubules.  Prophase marks the beginning of the formation of the spindle apparatus. During metaphase, the kinetochore microtubules align the chromosomes in the middle of the cell. During anaphase, the kinetochore microtubules pull the sister chromatids to opposite ends of the spindle poles. The spindles then disintegrate during telophase.
There are hundreds of microtubule associated proteins (MAPs) involved in the structure and formation of spindles. These proteins also ensure correct functioning of the spindle apparatus, which is vital in cell division. If there are any defects in the structure, formation or function of the spindle, it can lead to various complications such as abnormal numbers of chromosomes in the daughter cells, and consequently result in diseases such as Down Syndrome.  Defects or disruptions in mitotic spindles can also lead to neurological diseases such as Alzheimer's disease. 
The advancement in technology over the past century has enabled scientists to gain more insight into cell division and its various components such as spindle formation. There is still more to learn, and through ongoing research, scientists hope to shed more light on the filaments, proteins and motors that play vital roles in the structure and function of the spindle apparatus.
Study of cells began in 1665 when Robert Hooke discovered cells in cork bark tissue.  Subsequently, many others have used microscopes to study cells. However it was not until the 1800s that cell division was studied in more detail, with various different components of cells and phases of cell division being gradually discovered by various people. Since the topic of this wiki page is about spindle apparatus, the table below contains a timeline of discoveries starting from when the spindle apparatus was first recognised.
Brief Timeline of Some Historical Research On Spindle Apparatus
|1873||Hermann Fol discovered the spindles and astral rays. He used the analogy of magnetic field lines to describe the appearance and force of spindles as it moves the chromosomes during cell division. |
|1875||Eduard Strasburger independently researched cell division in plants and produced detailed images of plant cells undergoing cell division. His drawings portray the spindle fibers during the stages of cell division, which he published in his book Über Zellbildung und Zelltheilung ("On Cell Formation and Cell Division") in 1876. |
|1876|| Otto Bütschli observed fibrillar structures near the poles during cell division. He called these fibrillar structures ‘pole aster’. (We now call this the spindle apparatus). 
|1882|| Walther Flemming summarises his understanding and discoveries about mitosis in his book Zellsubstanz, Kern und Zelltheilung (‘Cell substance, nucleus and cell division’). He used the term ‘mitosis’, which is a Greek word meaning ‘thread’, to represent the shape of the chromosomes seen during mitosis.  He drew detailed diagrams of mitosis, in which the spindles can be seen pulling the chromosomes.
|1888||Theodor Boveri discovered that the ‘threads of aster’ (which we now call spindles) were controlled by ‘centrosomes’ (which we now call centriole). |
|1938||Becker researched mitosis in plant cells. Becker believed that the mitotic spindle originates from substances in the nucleus. |
|1952||Shinya Inoué researched the effect of colchicine on the structure of mitotic spindles. The results showed that colchicine caused a general decrease in the length of the spindles, and a loss of birefringence near the spindle poles. Shinya Inoué also researched on the effect of temperature on the birefringence of spindles.  It was observed that treating the Chaetopterus oocytes with low temperature resulted in the immediate abolishment of the birefringence of mitotic spindles.|
|1953||Hindmarsh wrote an article about the effect of colchicines on spindles of root tip cells.  It was written in observation that spindles do not have normal formation if cells are treated with colchicine. When the cell is treated with colchicine while undergoing cell division, it results in the breakdown of the spindle apparatus. The breakdown of the spindle apparatus leads to the abnormal disorganisation of chromosomes in cell division.|
|1957|| Bajer conducted a research on the origin of the spindle during mitosis in endosperm.  His observations lead him to believe that spindles originate from the "clear zone" (a semi-liquid substance that mainly originates from the cytoplasm) that forms around the nucleus in prophase.
|1966|| Bajer and Allen conducted a research on the structure and organisation of mitotic spindles in Haemanthus endosperm.  They observed that spindle fibers extend from the kinetochores to the polar region, and that each individual spindle fibres consisted of bundles of smaller filaments, and that these filaments intermingle as they approach the polar region. The intermingling of the filaments increase in metaphase and anaphase. When the spindle fibers are 5-10 microns long, the chromosomes stop moving and the spindles fibers then disappear.
|1967|| Nicklas and Staehly researched on the mechanics of chromosome attachment to the spindles.  They manipulated the chromosomes by poking them with glass needles to pull them away from the spindles, in order to observe how the kinetochores capture the chromosomes.
|1969||Nicklas and Koch did some further studies on how chromosomes attach to spindles by manipulating the position of the chromosomes to see the mechanism of attachment.  They demonstrated the importance of tension of spindle fibers in the beginning of anaphase.|
|1969||Manton et al. researched on the structure and development of spindles during meiosis and mitosis of marine diatom Lithodesmiumundulatum and published two articles to discuss their observations. Their first article discusses mitosis in spermatogonia.  The second article is about the early meiotic stages in male gametogenesis.  They concluded that there is a probability that 'polar plates' may be the source of growth for spindle microtubules.|
|1970||Manton et al. did some further research on the structure and development of spindles during meiosis and mitosis of marine diatom Lithodesmiumundulatum and published two more articles to discuss their observations.   It has been noted that the distribution of the spindles in mitosis and meiosis are similar. However the the number of microtubules seem to be greater in spermatogonium than in mitosis.|
|1971|| McIntosh et al. conducted a research about the distribution of spindle microtubules during mitosis in cultured human cells. They have noted different ratios of microtubule distribution in the spindles as it passes through the different phases of mitosis. The highest ratio of microtubules in each half spindle seems to occur in metaphase. 
Szollosi et al. researched about centrioles and their role in spindle apparatus formation.  Oocytes of rat, mice, hamster, Mongolian gerbils, and humans were used in this study. Centrioles were present in human oogonia, as well as the neonatal ovaries of rats. However, centrioles seem to be absent in later stages of oogenesis. It was not discovered what happens to the centrioles, because there was no observation of them breaking down. The results indicate that an intact centriole is not needed for successful completion of meiosis.
|1973||R.E. Stephens researched mitotic spindle thermodynamics and equilibrium during metaphase.  Sea urchin eggs undergoing metaphase were used in this study. These eggs were observed using polarization microscopy. The author of this article investigated the equilibrium of spindle fibres that are dependent on temperature. Rise of temperature seems to cause an increase in birefringence. Birefringence is also related to the proportion of tubulin content of microtubules.|
Inoué et al. researched about the effect of porcine brain tubulin on the growth and lability of mitotic spindles of chaetopterus oocytes. Their results showed that injecting the tubulin-PEG into the chaetopterus oocytes improved the spindle and aster birefringence. 
|1983||R.B. Nicklas researched the measurements of force produced by spindles during anaphase of mitosis.  Twelve experiments were performed on grasshopper spermatocytes. The results showed the relationship between the velocity of chromosomes and the opposing forces of the spindles. It was found that the spindles produce a large force, which shows that it can affect the stability and length of microtubules.|
|1984|| Ford studied spindle microtubular dysfunction in mothers who have children with Down Syndrome.  He describes how parents with dysfunctional spindle microtubules (which can lead to hyperploidy in mitosis and meiosis) results in Down Syndrome in the offspring of such individuals.
|1990||Krawczun et al. studied the reassembly of spindle microtubules in cells taken from patients of Alzheimer's Disease and Down Syndrome.  Research shows evidence that patients with Alzheimer's disease have impairments in the assembly of spindle microtubules.|
|1990|| Hayden et al. studied the mitotic spindles in newt lung cells. They discovered that chromosome attachment occurs when the kinetochore interact with astral microtubules. 
|1991|| Cassimeris and Salmon studied mitotic spindles in newt lung cells. They observed that kinetochore microtubules are shortened due to the loss of tubulin subunits near the kinetochore when the chromosomes are moving towards the pole. 
|1993||Mastronarde et al. studied interpolar spindle microtubules in PTK cells. They observed that there is a change in the arrangement of the plus ends of the interpolar microtubules during mid to late Anaphase B. However, the minus ends did not seem to change much in position during these phases. When sister chromatids are separated, the minus ends of many of the interpolar spindle microtubules become released from the kinetochore microtubules which makes it possible for the kinetochore microtubules and the spindle poles to be moved away from the interpolar microtubules when elongation of the spindles occur. |
|1994|| Cassimeris et al. researched about microtubule assembly in monopolar spindles of vertebrate.  They observed that there is not much significant difference between the microtubule distribution in monopolar and bipolar spindles in vertebrates. They also concluded that The molecular mechanisms for the movement of chromosomes caused by monopolar spindles is the same as bipolar spindles.
|1996||Williams et al. published a research article on the effect of mutations in the Drosophilia ZW10 gene.  The attachment of the bipolar spindles affect the redistribution of the ZW10 gene. Mutations in this gene leads to irregularities in chromosomal segregation, as well as disrupting normal chromosome behaviour in both mitosis and meiosis.|
|1997|| Watanabe et al. researched the effect of intracellular pH on mitotic spindle apparatus.  Fertilized eggs of Scaphechinus mirabilis and Clypeaster japonicus were used in this study. The results showed that the mitotic spindles increased to their maximum size at pHi 6.70. However, the spindle length then decreased when the pHi was changed from 6.70 to 7.84. The main result found overall from this research was that a slightly acidic pH results in the stabilization of microtubules in the spindles, and the number of microtubules present were larger than it is in normal eggs.
|1999||Carazo-Salas et al. conducted experiments on the formation of mitotic spindles induced by chromatin.  They demonstrated that the RCC1 protein (which is a chromosome associated protein) is required in the formation of the mitotic spindle. They proposed that the “high local concentration of Ran-GTP around chromatin” is generated by the RCC1 protein; this causes the “local nucleation of microtubules.” |
|2005||Bringmann studied the role of the spindle midzone in cytokinesis.  This study supported the earlier findings of other scientists, that the spindle midzone is not necessary for the completion of cytokinesis. However, aster-positioned cytokinesis has been shown to have a negative effect from the spindle midzone because of the competition between the aster-positioned and midzone-positioned furrows which “compete for contractile elements”.|
|2011||Hegarat et al. conducted a research study which demonstrated that both Aurora A and Aurora B work together to cause segregation of chromosomes during anaphase through depolymerisation of spindle microtubules. |
As reviewed in Glotzer (2009), the spindle apparatus is made from a combination of microtubules, motors and microtubule associated proteins (MAPs).  Microtubules that make up spindles are cylindrical polymers that are assembled from dimers of alpha-tubulin and beta-tubulin. They are polar filaments that have a fast-growing plus end and a slow-growing minus end that is often capped by the gamma-tubulin ring complex, a ring-shaped microtubule nucleator.
In most animal cells microtubules are nucleated at the centrosomes found at the spindle poles. However, it has been observed that spindles can still form in cells lacking centrosomes. The results show that non-centrosomal microtubules contribute to to spindle formation even in cells with centrosomes. These cells expressed GFP-alpha-tubulin. 
Types of microtubules
During metaphase, the mitotic spindle is comprised of kinetochore fibres, astral microtubules and interpolar microtubules. The kinetochore microtubules are connected to the chromosomes,  the astral microtubules  anchor the pole ends in position while the polar microtubules form the structure of the spindle apparatus.  The fusiform shape of the spindle is the result of the microtubule minus ends focusing at the poles and by cross-linking interpolar microtubules in an overlapping region situated in the midzone. A recent study has shown that the bending of astral microtubules may lead to asymmetric spindle formation. 
In the spindle, kinetochore microtubules have their plus ends embedded in the kinetochores of the sister chromatids and their minus ends at the spindle pole. Kinesins are important to maintain spindle bipolarity.  The simulataneous Kinesin inhibitor (KinI) induced disassembly at both the plus and minus ends may result in the poleward driving forces. GTPase Ran and its exchange factor, Regulator of chromosome condensation 1(RCC1), have been shown to induce microtubule polymerization around chromosomes and allows for chromatin induced mitotic spindle formation. 
Midzone and midbody
The kinetochore forms bivalent attachments with the spindle microtubules and the kinteochores position themselves correctly with respect to the division plane of the cell during anaphase.  Bivalent attachment of the sister chromatids to the spindle is achieved when the plus ends of the microtubules emanating from each pole interacts with the kinetochores of each sister pair and then becomes embedded. At the beginning of anaphase, the kinetchore fibres shorten ( delivering sister chromatids to the poles) and astral microtubules elongate . The region between the two poles is called the spindle midzone and the microtubules that populate this region are called midzone microtubules.  The term central spindle refers to the structure at the centre of the midzone, where the plus ends of the microtubules interdigitate. The microtubules of the central spindle eventually lose their interaction with the spindle poles. As the formation of the cleavage furrow progresses, the central spindle becomes compacted dense structure known as a the midbody. 
Role of microtubule associated proteins in spindle structure
The diverse functions of microtubule associated proteins greatly determine the structure of the microtubules. It is well established that CAP-GLYdomain containing linker protein 170/Microtubule plus-end tracking protein 1 (CLIP-170/Tip1) localizes to the kinetochore.The plus-end microtubule binding proteins ( +TIP) play a significant role in the regulation of microtubule stability and cell polarity during interphase. Research suggests that the +TIP protein Tip1 affects directly or indirectly the movement of the chromosomes towards to the poles during anaphase  .
Partially reducing xenophus microtubule associated protein 215 (XMAP215) or knocking out its homologues, ZYG-9 and Msps, disrupts spindle assembly or causes the formation of very small spindles   . Furthermore, Stathmin 1/oncoprotein 18 (Stathmin/ Op18) is family of destabilising proteins, and when the concentration of nonphosphorylatable Stathmin/ Op18 is increased, shorter spindles are formed. This provides evidence to suggest that microtubule catastrophe frequency and growth rate can determine spindle length.  Studies also show that spindles formed in the presence of a total depletion of XMAP230/XMAP4 had fewer or no interpolar microtubules and were of decreased width. 
Astral microtubules play a large role in determining the plane of division. They are part of the spindle-dependent mechanism that induces formation of the cleavage apparatus as a cortical ring encircling the mitotic spindle.As a result, cytokinesis always cleaves the cell between the separated chromosomes independent of spindle orientation within the cell body. As mentioned before, astral microtubules play a central role during asymmetric cell division due to the interaction of astral microtubules with cortical actin, as well as nonactin cortical factors . In this case, the interactions of the astral microtubule cortex generate forces that align the spindle parallel to the cell polarity axis so that the astral microtubule-induced cleavage apparatus bisects both separated chromosomes and polarized material. Therefore, astral microtubules ensure accurate chromosome segregation and determine the amount of symmetry by establishing and coordinating positions of the cleavage plane and spindle.
Mitotic spindle is made up of spindle microtubules which anchor at the end of both centrosomes and kinetochores. When mechanical force is generated, chromsomes will be separated and pulled to opposite poles towards the centromeres by the spindle apparatus. In the spindle, kinetochore microtubules have their plus ends embedded in the kinetochores of the sister chromatids and their minus ends at the spindle pole. A range of proteins are also participating and helping spindle apparatus to perform its three major sets of functions which are chromosome alignment, chromosome segregation and bipolarity.
The spindle apparatus is responsible for the alignment of chromosomes at the onset of metaphase. During prometaphase, the chromosomes attached to the mitotic spindle eventually align halfway between the two spindle spindle poles. This is called the metaphase plate. The forces keeping the chromosomes at the plate is still unclear however it is thought that the continuous growth and shrinkage of the microtubules and the actions of the microtubule associated proteins may be involved. This creates and equilibrium allowing for the chromosomes to remain aligned. As reviewed in Wordeman (2008), studies have shown that kinesin 8 and kinesin 13 are enriched near the centrosomes and centromeres and are involved in modulating the kinetics of microtubule assembly and disassembly from free tubulin dimers.
Furthermore, research that is done by Itoh et al show that Nucleoporin 188 kDa (Nup188) has a function of regulating chromosome alignment.  It was discovered early on with the use of a novel organelle trap assay. Nup188 does the regulation by localizing to spindle poles of the spindle apparatus during mitosis. On Nup188, the middle and the C-terminal regions are necessary for chromosome alignment function. Therefore, their experimental procedure uses Nup188-depleted mitotic cells and it was observed that that chromosomes are unable to align at the metaphase plate . Adding to that, microtubule bundles were hardly formed and attached to kinetochores in Nup188-depleted cells. Their study also found that Nup188 interacts with NuMA , its job being to focus all the microtubules to chromosomes. Furthermore, the localization of microtubules towards the spindle is disrupted in Nup188-depleted cells. Their results suggest that Nup188 helps chromosome alignment through K-fiber formation. 
The spindle poles also segregate the separated sister chromatids during anaphase. All the chromatids move apart at the same speed due to two processes involving the mitotic spindle called anaphase A and anaphase B which occur simultaneously. In anaphase A, microtubule associated proteins operate at the kinetochore to shorten the kinetochore microtubules through depolymerisation. This causes the chromatids to move poleward .
In anaphase B, the spindle poles themselves move apart therefore contributing to chromosome segregation . Kynesin and dynein families operate on different types of spindle fibers to provide the driving force. For example, the kinesin-5 motor proteins require contact with another microtubule for it to cross-link with and push against for it to activate and become an ATP hydrolysing directional motor that drives spindle elongation. It acts on the interpolar microtubules and causes them to slide from opposite poles past one another at the spindle equator, therefore pushing the spindle poles apart. 
Furthermore, Lorson et al have found that lin-5 gene encodes a protein that with a central coiled-coil domain also has a special function that can localize to the spindle apparatus and help chromosome segregation and spindle movements. It is found at the centrosomes throughout mitosis and at the spindle during meiosis. Its functions are associating with microtubule and cell-division circle.They have manipulated the experiment and shown that the spindle fails to position itself or to move the chromosomes when lin-5 function is knocked down. Their results also show that lin-5 is involving with cytoplasmic cleavage and correct alternation of the S and M phases of the cell cycle. All in all, spindle migration and chromosome movements depend on the tiny mechanical forces that are generated by many different numbers of motor proteins associating with microtubule assembly and disassembly. 
The following diagrams of mitosis show the stages of cell division, and the role of spindles in the relevant stages.
Stages of Cell Division and Role of Spindles in Each Stage
Bipolarity of the spindle is critically important for correct segregation of the chromosomes and kinesin Eg5, (a plus ended kinesins 5 molecules) is responsible for allowing this spindle function. The exact mechanism by which this occurs is still not conclusive. However, the motor domains favour the second bound microtubule to be in an anti-parallel orientation and this may contribute to the formation of the bipolar spindle. Bipolarity of the spindles ensure the chromosomes separate with the highest fidelity possible.
Further study that is done by Simeonov et al has shown that Kinesin-14 and Kinesin-5 regulate spindle assembly and maintenance. Their maintenance is critical to genomic fidelity in daughter cells during cell division. However, Kinesin-5 and Kinesin-14 play very different roles. Kinesin-5 is thought more of to stabilize and slide interpolating microtubules from adjacent poles. It also allows maintenance of spindle length. Kinesin-14 proteins are found similar among eukaryotes. They’re able to localize to multiple spindle sites and take part in a lot of spindle roles. In mitotic spindle bipolarity, Kinesin-14 were investigated and thought to be counterbalancing Kinesin-5 forces in spindle bipolarity. Kinesin-14 usually locate to multiple spindle sites including poles, kinetochores and microtubule bundles. It also contributes to other important cell division events including regulating microtubule organization, kinetochore interactions, anchoring microtubules and microtubule sliding. 
Mechanism of Formation
The spindle itself is defined by microtubule nucleation occurring mainly at the two centrosomes. The microtubules aid in organising the spindle as well as its function in segregating chromosomes into two daughter cells. When a spindle is properly assembled, the sets of chromosomes are aligned along the central equator of the cell. Microtubules align perpendicular and kinetochores attach to its plus ends with the minus-ends embedded at the cell poles. It is crucial that the alignment is correct so that the cell division occurs correctly. Up to this point, there has been a development of two generally accepted spindle assembly models which explain the mechanism of formation of the spindle apparatus: Search and capture, and Microtubule Self-Organisation. 
The Search and Capture model involves microtubules nucleating from centrosomes, chromosomes and kinetochores simply by chance and become stabilised to form a spindle. The Microtubule Self-Organisation model on the other hand depicts randomly orientated microtubules that undergo nucleation with the absence of centrosomes being organised into bipolar arrays by microtubule organising proteins (MOPs). 
Search and Capture model
Due to the centrosomes, microtubules end up nucleated and form symmetrical asters (star shapes). They are relative unstable and due to this condition, will "search" the cytoplasm by alternating between growing and shrinking phases. This alternation between growing and shrinking phases is known as dynamic instability, which occurs during microtubule assembly. In essence, tubulin-bound GTP is hydrolysed into GDP and the energy released causes the microtubules to become unstable. In mitosis, this is crucial because the accurate attachment of chromosomes to the spindles to allow the formation of the metaphase plate. The "capture" part occurs when a kinetochore attaches to the searching microtubule. The kinetochore attachment turns to an end by microtubule bundle association. The unattached end is then attached to a microtubule from the opposite pole. This leads to the chromosome moving towards the congression (or the metaphase plate). The chromosome eventually will oscillate there and cell division can begin.
Microtubule Self-Organisation model
This model, also known as "self-assembly", states that after the breakdown of the nuclear envelope of the cell, microtubules have the ability to grow from various sites around the now condensed chromatin and "self-organise" into a spindle apparatus. This is regardless of the absence of centrosomes or microtubule-organizing centres. It also suggests that it is the chromosomes themselves that can nucleate microtubules (not centrosomes as the search and capture model suggests) and organise them into bipolar arrays. This is done by stimulating the signalling cascades of the Ran-GTP and the CPC (chromosomal passenger complex) pathway.
The Ran-GTP cascade (mediated by the nuclear transport factor importin β) releases spindle assembly factors (also known as SAFs ) and promotes the formation of the spindle by organizing microtubules in the vicinity of chromosomes. The CPC pathway generates an Aurora B signal which stimulates microtubule assembly located around the chromosomes and does so by locally inhibiting factors that decrease the chances of microtubule catastrophes catastrophes.
The roles of actin filaments in mitotic spindles
A study by Woolner et al(2008) searches the roles of actin filaments (F-actin) and F-actin-based motors ( myosins ) which are required components of mitotic spindles. In their research, they found out that myosin-10 (Myo10) is important for assembly of meiotic spindles. In more detail, Myo10 set themselves to mitotic spindle poles and is very important for proper spindle anchoring, normal spindle length, spindle pole integrity as well as progression through metaphase. They also found out the antagonistic relationship between F-actin and Myo10 in THE maintenance of spindle length and that they work independently. Actin filaments (F-actin) and F-actin-based motors (myosins) are essential components in the proper functioning of spindle apparatus. They are required for correct positioning of the spindle towards the anchor point.
Furthermore, another recent study conducted by Rump et al(2011) found out the function of the long-tailed class-1 myosin, myosin-1C, from Dictyostelium discoideum during mitosis. They use the data obtained as back up, suggesting that myosin-1C binds to microtubules and play a part in maintenance of spindle stability during chromosome separation and that the association of myosin-1C with microtubules is mediated through the tail domain. Further data has lead to another suggestion that myosin-1C tail can inhibit kinesin motor activity, strengthen the stability of microtubules as well as forming crosslinks between microtubules and F-actin.  Myosin-1C motor and tail-domain-mediated MT-F-actin are required for the re-localization of certain proteins from the cell periphery to the spindle. Therefore, both contribute to the formation and stability of spindle apparatus a considerable amount.
By combining the use of force-calibrated needles, high-resolution microscopy, and biochemical perturbations, recently researchers analyzed the vertebrate metaphase spindle and found that spindle viscosity is dependent on microtubule density and cross-linking. Spindle elasticity are said to be related to kinetochore and non-kinetochore microtubule rigidity, and also to spindle pole organization by kinesin-5 and dynein.  The data obtained in their research provides micromechanics modal insight of this cytoskeletal architecture and provides insight into how structural and functional stability is maintained for proper control of spindle function.
Spindle assembly during the the gradual transition from meiosis to mitosis
In a study performed by Courtois et al , spindle apparatus assembly during transition from meiosis to mitosis was researched. The transition from meiosis to mitosis occurs during embryonic development, and is a very important topic of research. The mechanisms through which the spindle assembly changes during this transition has not been researched in detail in the past. Hence the authors wished to research in this area. They used mouse embryos in their study. The first cleavages showed that spindle formation mechanisms in mitosis is the same as it was during meiosis. The spindles appear to assemble by themselves from microtubule-organizing centers that are distributed randomly, not from centrioles. This occurs due to the activities of kinesin-5 and dynein. During development in preimplantation, the number of microtubule-organizing centers gradually decrease, and the pole of the spindles become focused. The length of the spindles also adjust in size in accordance to the cell size.
Role of Aurora A in Central Spindle Assembly
Central spindle assembly requires a multitude of proteins, one of them being the regulatory protein, Aurora A . Reboutier et al has chosen to focus on Aurora A in their study and its involvement in central spindle assembly.  Previously, the functions of Aurora A after metaphase was not known. Hence the authors were particularly interested to research about the function of Aurora A after metaphase. They observed the role of Aurora A in the transition from metaphase to anaphase. They discovered that Aurora A is needed for spindle assembly in anaphase through the process of "phosphorylation of Ser 19 of P150Glued ".  When Aurora A was inhibited, it caused defects in central spindle assembly. In one of their experiments, they treated AS-AurA cells with 1-Na-PP1 during Anaphase. This caused the chromosomes to stop moving, and the cell did not move onto the telophase stage, or undergo cytokinesis. This resulted in binucleated cells.
Correct alignment of the mitotic spindle during division is vital for cell fate determination, tissue organization and development. Mutations causing brain diseases and cancer in humans and mice have been associated with spindle orientation defects. These defects are thought to lead to an imbalance between symmetric and asymmetric divisions, causing reduced or excessive cell proliferation.
The central nervous system of vertebrates is the results of a series of symmetric and asymmetric cell divisions.  Spindles parallel to the apical plane will give rise to planar, symmetric (and proliferative) divisions, whereas vertical or oblique spindles will result in asymmetric (and differentiative) divisions.  This implies that if spindle orientation were to favour oblique spindles, then neurogenesis will occur at the expense of stem cell pool expansion, leading to smaller brains.
Primary microcephaly (MCPH) is an autosomal, recessive disease which is characterised by reduction in brain size. All of the MCPH proteins can localize to centrosomes and are involved in centriole biogenesis, centrosome maturation, and spindle organization   . The most commonly affected gene is ASPM (abnormal spindle-like microcephaly associated, MCPH5). In human culture cells, ASPM localizes to centrosomes and spindle poles . Depletion of ASPM leads to spindle misorientation . A mutation in ASPM identified in microcephalic patients impairs the ability of ASPM to localize to centrosomes. Patients bearing microcephaly are mentally retarded but do not display other neurological disorders.
The lissencephalic brain is characterised by reduction in brain size with an almost smooth surface and a abnormal organization of the neocortex.The Lis 1 gene is responsible for stabilising microtubules via dynein-dynactin complex .Therefore, it is responsible for pulling the entire spindle at the cell cortex . Depletion of Lis1 results in less stable astral microtubules and loss of dynein cortical localization in mouse . The mitotic spindle then becomes deflected from a horizontal position leading to premature defects .
Aneuploidy in neuronal cells accounts for 90% of the loss of neurons in the brains of patients with Alzheimer's disease. Inhibition of specific microtubule motors causes disruption of mitotic spindles.  Such defects have been found to cause aneuploidy which leads to neurodegeneration in Alzheimer's disease. 
Spindle orientation defects may lead to cell hyperplasia y suppressing the asymmetric, differentiative divisions of stem cells while increasing their symmetric, proliferative divisions  . Also, evidence reviewed by McAllister et al (2010) suggests that defective spindle orientation might disorganize tissue architecture, a typical feature of malignant transformation 
APC - Adenomatous polyposis coli
A vast majority of colon cancers and familial adenomatous polyposis disease show a mutation in the apc gene. These mutations may predispose patients to intestinal cancer  . APC also plays a crucial role during mitosis, where it binds the microtubule plus end scaffold protein EB1  to promote microtubule stability   . Deletions or mutations of APC causes spindle positioning and chromosome alignment defects leading to instability of the chromosomes and cytokinesis failure in animal cells     .
Dysfunction of spindle microtubules can lead to hyperploidy during mitosis and meiosis.  This can result in Down Syndrome in the children of parents with such dysfunctional spindle microtubules.
Actin: Actin is a globular multi-functional protein that forms microfilaments.
Anaphase: The stage during cell division when kinetochore microtubules pull the sister chromatids to opposite ends of the spindle poles.
Aneuploidy: abnormal number of chromosomes
ASPM: abnormal spindle-like microcephaly associated MCPH5 gene
Aurora A: kinase also known as serine/threonine-protein kinase 6 is an enzyme that in humans. It is implicated with important processes during mitosis and meiosis whose proper function is integral for healthy cell proliferation
Aurora B: It is a kinase protein that function in the attachment of the mitotic spindle to the centromere
Centrosomes: organelle that serves as the main microtubule organizing center(MTOC) of the animal cell as well as a regulator of cell-cycle progression
Cell Division: The process through which cells divide to duplicate itself.
Cleavage furrow: indentation of the cell's surface that begins the progression of cleavage, by which animal and some algal cells undergo cytokinesis, the final splitting of the membrane, in the process cell division.
CLIP-170/Tip1: It is a cytoplasmic linker protein (CLIPs). (CLIPs) are members of the plus-end-binding protein family (+TIPs) that interact with the growing plus ends of microtubules. They modulate microtubule dynamics and are proposed to link this cytoskeletal network to other intracellular structures.
CPC : chromosomal passenger complex pathway. It is composed of Aurora B kinase and its regulatory subunits INCENP, Survivin, and Borealin. The pathway modulates multiple events during mitosis
Cytokines: are small signaling molecules used for cell signaling.
Cytokinesis: process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells
Dictyostelium discoideum: a species of soil-living amoeba belonging to the phylum Mycetozoa.
GFP : Green fluorescence protein which exhibits bright green fluorescencewhen exposed to light in the blue to ultraviolet range. It is used as a biomarker.
GTPase RAN : (RAs-related Nuclear protein)Ran is a GTP binding protein that is essential for the translocation of RNA and proteins through the nuclear pore complex. The Ran protein is also involved in control of DNA synthesis and cell cycle progression.
Hyperplasia: increase in number of cells/proliferation of cells
Kinesin: protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP (thus kinesins are ATPases
Kinetochores: protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.
Lis1: Lissencephaly causative gene
MAPs (Microtubule Associated Proteins): Specific proteins that interact with the microtubules of the cellular cytoskeleton.
Meiosis: A type of cell division where the parent cell produces 4 daugher cells that are not identical to the parent cell.
Metaphase: stage of mitosis in the eukaryotic cell cycle in which condensed and highly coiled chromosomes, carrying genetic information, align in the middle of the cell before being separated into each of the two daughter cells.
Microtubule : component of the cytoskeleton, found throughout the cytoplasm
microtubule catastrophes : The switch from growth to shrinking
Mitosis: A type of cell division where the parent cell produces two exact copies of daughter cells.
MOPs: Microtubule organising proteins
Myosins: comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes.
Neurogenesis: the process by which neurons are generated from neural stem and progenitor cells
Nucleator : A site of polymer assembly
nuclear transportin factor beta: facilitates protein transport into the nucleus
P150Glued: polypeptide that copurifies with cytoplasmic dynein
Prometaphase: phase of mitosis following prophase and preceding metaphase, in eukaryotic somatic cells.
Prophase: Stage of cell division in eukaryotic cells during which Chromosomes coil, nuclear membrane disintegrates, and spindle fibres (microtubules) form.
RCC1 : Regulator of chromosome condensation 1
SAF : Spindle assembly factors.
Ser 19: an anti-myosin light chain antibody
Spindle Apparatus: Thread-like structures in cells which forms during cell division in order to separate the chromosomes to the opposite poles.
Stathmin/ Op18: Stathmin 1/oncoprotein 18, also known as STMN1, is a highly conserved 17 kDa protein. Its function as an important regulatory protein of microtubule dynamics has been well characterized
Stem cell: biological cells found in all multicellular organisms, that can divide (through mitosis) and differentiate into diverse specialized cell types and can self-renew to produce more stem cells
Telophase: final stage in both meiosis and mitosis in aeukaryotic cell. Two daughter nuclei form in each daughter cell, and phosphatases de-phosphorylate the nuclear lamins at the ends of the cell, forming nuclear envelopes around each nucleus
XMAP: Xenophus Microtubule Assembly Protein
- Spindle structure.jpg
The three classes of microtubules in a mitotic spindle in an animal cell
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.
- Michael Glotzer The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat. Rev. Mol. Cell Biol.: 2009, 10(1);9-20 PubMed 19197328
- Go Itoh, Shiro Sugino, Masanori Ikeda, Mayumi Mizuguchi, Shin-ichiro Kanno, Mohammed A Amin, Kenji Iemura, Akira Yasui, Toru Hirota, Kozo Tanaka Nucleoporin Nup188 is required for chromosome alignment in mitosis. Cancer Sci.: 2013, 104(7);871-9 PubMed 23551833
- M A Lorson, H R Horvitz, S van den Heuvel LIN-5 is a novel component of the spindle apparatus required for chromosome segregation and cleavage plane specification in Caenorhabditis elegans. J. Cell Biol.: 2000, 148(1);73-86 PubMed 10629219
- Dimitre R Simeonov, Katelyn Kenny, Lan Seo, Amanda Moyer, Jessica Allen, Janet L Paluh Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity. Cell Cycle: 2009, 8(21);3571-83 PubMed 19838064
- J H Hayden, S S Bowser, C L Rieder Kinetochores capture astral microtubules during chromosome attachment to the mitotic spindle: direct visualization in live newt lung cells. J. Cell Biol.: 1990, 111(3);1039-45 PubMed 2391359
- L Cassimeris, E D Salmon Kinetochore microtubules shorten by loss of subunits at the kinetochores of prometaphase chromosomes. J. Cell. Sci.: 1991, 98 ( Pt 2);151-8 PubMed 2055954
- D N Mastronarde, K L McDonald, R Ding, J R McIntosh Interpolar spindle microtubules in PTK cells. J. Cell Biol.: 1993, 123(6 Pt 1);1475-89 PubMed 8253845
- Claire E Walczak, Rebecca Heald Mechanisms of mitotic spindle assembly and function. Int. Rev. Cytol.: 2008, 265;111-58 PubMed 18275887
- Sharat Gadde, Rebecca Heald Mechanisms and molecules of the mitotic spindle. Curr. Biol.: 2004, 14(18);R797-805 PubMed 15380094
- J H Ford Spindle microtubular dysfunction in mothers of Down syndrome children. Hum. Genet.: 1984, 68(4);295-8 PubMed 6239816
- Antoneta Granic, Huntington Potter Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis. PLoS ONE: 2013, 8(4);e60718 PubMed 23593294
- Robert Hooke. "Micrographia: or, Some physiological descriptions of minute bodies made by magnifying glasses". London: J. Martyn and J. Allestry, 1665. (first edition).
- Bechtel, W. (2005). Discovering Cell Mechanisms: The Creation of Modern Cell Biology. Cambridge University Press. pp. 75
- Strasburger, E. (1876). Über Zellbildung und Zelltheilung ("On Cell Formation and Cell Division"). H. Dabis.
- Bütschli, O. Studien über die ersten Entwicklungsvorgänge der Eizelle, der Zellteilung und die Conjugation der Infusorien. Abh. Senckenbergische Naturf. Ges. 10, 213–452 (1876) as reviewed in N Paweletz Walther Flemming: pioneer of mitosis research. Nat. Rev. Mol. Cell Biol.: 2001, 2(1);72-5 PubMed 11413469
- Flemming, W. (1882) Zellsubstanz, Kern und Zelltheilung. F.C.W. Vogel. Leipzig [as reviewed in N Paweletz Walther Flemming: pioneer of mitosis research. Nat. Rev. Mol. Cell Biol.: 2001, 2(1);72-5 PubMed 11413469 ]
- Windelspecht, M. (2003). Groundbreaking scientific experiments, inventions, and discoveries of the 19th Century. Greenwood Publishing Group. pp. 44
- Becker, W.A. (1938). Recent investigations in vivo on the division of plant cells. Bot. Rev. 4, 446-472.
- Inoué, S. (1952). The effect of colchicine on the microscopic and submicroscopic structure of the mitotic spindle. Exptl. Cell Res. Suppl. 2:305.
- Inoué, S. (1952).Effect of temperature on the birefringence of the mitotic spindle. Biol. Bull. 103:316.
- Hindmarsh, M. M. (1953). The effect of colchicine on the spindle of root tip cells. Proc. Litm. Soc. N.S.W. 77, 300-306.
- A BAJER Ciné-micrographic studies on mitosis in endosperm. III. The origin of the mitotic spindle. Exp. Cell Res.: 1957, 13(3);493-502 PubMed 13490367
- A Bajer, R D Allen Structure and organization of the living mitotic spindle of Haemanthus endosperm. Science: 1966, 151(3710);572-4 PubMed 5903581
- R B Nicklas, C A Staehly Chromosome micromanipulation. I. The mechanics of chromosome attachment to the spindle. Chromosoma: 1967, 21(1);1-16 PubMed 5339860
- R B Nicklas, C A Koch Chromosome micromanipulation. 3. Spindle fiber tension and the reorientation of mal-oriented chromosomes. J. Cell Biol.: 1969, 43(1);40-50 PubMed 5824068
- I Manton, K Kowallik, H A Von Stosch Observations on the fine structure and development of the spindle at mitosis and meiosis in a marine centric diatom (Lithodesmium undulatum). I. Preliminary survey of mitosis in spermatogonia. J Microsc: 1969, 89(3);295-320 PubMed 5819685
- I Manton, K Kowallik, H A von Stosch Observations on the fine structure and development of the spindle at mitosis and meiosis in a marine centric diatom (Lithodesmium undulatum). II. The early meiotic stages in male gametogenesis. J. Cell. Sci.: 1969, 5(1);271-98 PubMed 5389565
- I Manton, K Kowallik, H A von Stosch Observations on the fine structure and development of the spindle at mitosis and meiosis in a marine centric diatom (Lithodesmium undulatum). 3. The later stages of meiosis I in male gametogenesis. J. Cell. Sci.: 1970, 6(1);131-57 PubMed 5417690
- I Manton, K Kowallik, H A von Stosch Observations on the fine structure and development of the spindle at mitosis and meiosis in a marine centric diatom (Lithodesmium undulatum). IV. The second meiotic division and conclusion. J. Cell. Sci.: 1970, 7(2);407-43 PubMed 5530567
- J R McIntosh, S C Landis The distribution of spindle microtubules during mitosis in cultured human cells. J. Cell Biol.: 1971, 49(2);468-97 PubMed 19866774
- D Szollosi, P Calarco, R P Donahue Absence of centrioles in the first and second meiotic spindles of mouse oocytes. J. Cell. Sci.: 1972, 11(2);521-41 PubMed 5076360
- R E Stephens A thermodynamic analysis of mitotic spindle equilibrium at active metaphase. J. Cell Biol.: 1973, 57(1);133-47 PubMed 4734864
- S Inoué, G G Borisy, D P Kiehart Growth and lability of Chaetopterus oocyte mitotic spindles isolated in the presence of porcine brain tubulin. J. Cell Biol.: 1974, 62(1);175-84 PubMed 4407048
- R B Nicklas Measurements of the force produced by the mitotic spindle in anaphase. J. Cell Biol.: 1983, 97(2);542-8 PubMed 6885908
- M S Krawczun, E C Jenkins, K P Lele, E A Sersen, H M Wisniewski Study of spindle microtubule reassembly in cells from Alzheimer and Down syndrome patients following exposure to colcemid. Alzheimer Dis Assoc Disord: 1990, 4(4);203-16 PubMed 2148262
- L Cassimeris, C L Rieder, E D Salmon Microtubule assembly and kinetochore directional instability in vertebrate monopolar spindles: implications for the mechanism of chromosome congression. J. Cell. Sci.: 1994, 107 ( Pt 1);285-97 PubMed 8175915
- B C Williams, M Gatti, M L Goldberg Bipolar spindle attachments affect redistributions of ZW10, a Drosophila centromere/kinetochore component required for accurate chromosome segregation. J. Cell Biol.: 1996, 134(5);1127-40 PubMed 8794856
- K Watanabe, M S Hamaguchi, Y Hamaguchi Effects of intracellular pH on the mitotic apparatus and mitotic stage in the sand dollar egg. Cell Motil. Cytoskeleton: 1997, 37(3);263-70 PubMed 9227856
- R E Carazo-Salas, G Guarguaglini, O J Gruss, A Segref, E Karsenti, I W Mattaj Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature: 1999, 400(6740);178-81 PubMed 10408446
- Henrik Bringmann Cytokinesis and the spindle midzone. Cell Cycle: 2005, 4(12);1709-12 PubMed 16258282
- Nadia Hégarat, Ewan Smith, Gowri Nayak, Shunichi Takeda, Patrick A Eyers, Helfrid Hochegger Aurora A and Aurora B jointly coordinate chromosome segregation and anaphase microtubule dynamics. J. Cell Biol.: 2011, 195(7);1103-13 PubMed 22184196
- U S Tulu, N M Rusan, P Wadsworth Peripheral, non-centrosome-associated microtubules contribute to spindle formation in centrosome-containing cells. Curr. Biol.: 2003, 13(21);1894-9 PubMed 14588246
- Ivan V Maly Equilibria of idealized confined astral microtubules and coupled spindle poles. PLoS ONE: 2012, 7(6);e38921 PubMed 22719988
- Gregory C Rogers, Stephen L Rogers, Tamara A Schwimmer, Stephanie C Ems-McClung, Claire E Walczak, Ronald D Vale, Jonathan M Scholey, David J Sharp Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase. Nature: 2004, 427(6972);364-70 PubMed 14681690
- Sherilyn Goldstone, Céline Reyes, Guillaume Gay, Thibault Courthéoux, Marion Dubarry, Sylvie Tournier, Yannick Gachet Tip1/CLIP-170 protein is required for correct chromosome poleward movement in fission yeast. PLoS ONE: 2010, 5(5);e10634 PubMed 20498706
- R Tournebize, A Popov, K Kinoshita, A J Ashford, S Rybina, A Pozniakovsky, T U Mayer, C E Walczak, E Karsenti, A A Hyman Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts. Nat. Cell Biol.: 2000, 2(1);13-9 PubMed 10620801
- L R Matthews, P Carter, D Thierry-Mieg, K Kemphues ZYG-9, a Caenorhabditis elegans protein required for microtubule organization and function, is a component of meiotic and mitotic spindle poles. J. Cell Biol.: 1998, 141(5);1159-68 PubMed 9606208
- U Marklund, N Larsson, H M Gradin, G Brattsand, M Gullberg Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics. EMBO J.: 1996, 15(19);5290-8 PubMed 8895574
- B Cha, L Cassimeris, D L Gard XMAP230 is required for normal spindle assembly in vivo and in vitro. J. Cell. Sci.: 1999, 112 ( Pt 23);4337-46 PubMed 10564651
- S Strome Determination of cleavage planes. Cell: 1993, 72(1);3-6 PubMed 8422680
- M Bienz Spindles cotton on to junctions, APC and EB1. Nat. Cell Biol.: 2001, 3(3);E67-8 PubMed 11231588
- Linda Wordeman How kinesin motor proteins drive mitotic spindle function: Lessons from molecular assays. Semin. Cell Dev. Biol.: 2010, 21(3);260-8 PubMed 20109570
- B R Miller, M Powers, M Park, W Fischer, D J Forbes Identification of a new vertebrate nucleoporin, Nup188, with the use of a novel organelle trap assay. Mol. Biol. Cell: 2000, 11(10);3381-96 PubMed 11029043
- A Desai, P S Maddox, T J Mitchison, E D Salmon Anaphase A chromosome movement and poleward spindle microtubule flux occur At similar rates in Xenopus extract spindles. J. Cell Biol.: 1998, 141(3);703-13 PubMed 9566970
- Dhanya K Cheerambathur, Gul Civelekoglu-Scholey, Ingrid Brust-Mascher, Patrizia Sommi, Alex Mogilner, Jonathan M Scholey Quantitative analysis of an anaphase B switch: predicted role for a microtubule catastrophe gradient. J. Cell Biol.: 2007, 177(6);995-1004 PubMed 17576796
- Lukas C Kapitein, Erwin J G Peterman, Benjamin H Kwok, Jeffrey H Kim, Tarun M Kapoor, Christoph F Schmidt The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. Nature: 2005, 435(7038);114-8 PubMed 15875026
- Hanne Varmark Functional role of centrosomes in spindle assembly and organization. J. Cell. Biochem.: 2004, 91(5);904-14 PubMed 15034926
- Maurizio Gatti, Elisabetta Bucciarelli, Ramona Lattao, Claudia Pellacani, Violaine Mottier-Pavie, Maria Grazia Giansanti, Maria Patrizia Somma, Silvia Bonaccorsi The relative roles of centrosomal and kinetochore-driven microtubules in Drosophila spindle formation. Exp. Cell Res.: 2012, 318(12);1375-80 PubMed 22580224
- Siet M J L van den Wildenberg, Li Tao, Lukas C Kapitein, Christoph F Schmidt, Jonathan M Scholey, Erwin J G Peterman The homotetrameric kinesin-5 KLP61F preferentially crosslinks microtubules into antiparallel orientations. Curr. Biol.: 2008, 18(23);1860-4 PubMed 19062285
- Janet L Paluh [Kinesin-14 leaps to pole position in bipolar spindle assembly]. Ai Zheng: 2008, 27(9);989-92 PubMed 18799042
- T Gaglio, M A Dionne, D A Compton Mitotic spindle poles are organized by structural and motor proteins in addition to centrosomes. J. Cell Biol.: 1997, 138(5);1055-66 PubMed 9281583
- Ekaterina L Grishchuk, Maxim I Molodtsov, Fazly I Ataullakhanov, J Richard McIntosh Force production by disassembling microtubules. Nature: 2005, 438(7066);384-8 PubMed 16292315
- Claire E Walczak, Rebecca Heald Mechanisms of mitotic spindle assembly and function. Int. Rev. Cytol.: 2008, 265;111-58 PubMed 18275887
- A Chan, W Z Cande Maize meiotic spindles assemble around chromatin and do not require paired chromosomes. J. Cell. Sci.: 1998, 111 ( Pt 23);3507-15 PubMed 9811565
- Jeffrey B Woodruff, David G Drubin, Georjana Barnes Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle. Mol. Biol. Cell: 2012, 23(2);258-67 PubMed 22090343
- Boo Shan Tseng, Lei Tan, Tarun M Kapoor, Hironori Funabiki Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly. Dev. Cell: 2010, 18(6);903-12 PubMed 20627073
- M V Nachury, T J Maresca, W C Salmon, C M Waterman-Storer, R Heald, K Weis Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell: 2001, 104(1);95-106 PubMed 11163243
- Srinath C Sampath, Ryoma Ohi, Oliver Leismann, Adrian Salic, Andrei Pozniakovski, Hironori Funabiki The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell: 2004, 118(2);187-202 PubMed 15260989
- Sarah Woolner, Lori L O'Brien, Christiane Wiese, William M Bement Myosin-10 and actin filaments are essential for mitotic spindle function. J. Cell Biol.: 2008, 182(1);77-88 PubMed 18606852
- Agrani Rump, Tim Scholz, Claudia Thiel, Falk K Hartmann, Petra Uta, Maike H Hinrichs, Manuel H Taft, Georgios Tsiavaliaris Myosin-1C associates with microtubules and stabilizes the mitotic spindle during cell division. J. Cell. Sci.: 2011, 124(Pt 15);2521-8 PubMed 21712373
- Yuta Shimamoto, Yusuke T Maeda, Shin'ichi Ishiwata, Albert J Libchaber, Tarun M Kapoor Insights into the micromechanical properties of the metaphase spindle. Cell: 2011, 145(7);1062-74 PubMed 21703450
- Aurélien Courtois, Melina Schuh, Jan Ellenberg, Takashi Hiiragi The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development. J. Cell Biol.: 2012, 198(3);357-70 PubMed 22851319
- David Reboutier, Marie-Bérengère Troadec, Jean-Yves Cremet, Lucie Chauvin, Vincent Guen, Patrick Salaun, Claude Prigent Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued. J. Cell Biol.: 2013, 201(1);65-79 PubMed 23547029
- Elise Peyre, Xavier Morin An oblique view on the role of spindle orientation in vertebrate neurogenesis. Dev. Growth Differ.: 2012, 54(3);287-305 PubMed 22524602
- W B Huttner, M Brand Asymmetric division and polarity of neuroepithelial cells. Curr. Opin. Neurobiol.: 1997, 7(1);29-39 PubMed 9039800
- Mónica Bettencourt-Dias, Friedhelm Hildebrandt, David Pellman, Geoff Woods, Susana A Godinho Centrosomes and cilia in human disease. Trends Genet.: 2011, 27(8);307-15 PubMed 21680046
- Harald Löffler, Anne Fechter, Marc Matuszewska, Rainer Saffrich, Martin Mistrik, Joachim Marhold, Christin Hornung, Frank Westermann, Jiri Bartek, Alwin Krämer Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Res.: 2011, 71(6);2129-39 PubMed 21406398
- Natalay Kouprina, Adam Pavlicek, N Keith Collins, Megumi Nakano, Vladimir N Noskov, Jun-Ichirou Ohzeki, Ganeshwaran H Mochida, John I Risinger, Paul Goldsmith, Michelle Gunsior, Greg Solomon, William Gersch, Jung-Hyun Kim, J Carl Barrett, Christopher A Walsh, Jerzy Jurka, Hiroshi Masumoto, Vladimir Larionov The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum. Mol. Genet.: 2005, 14(15);2155-65 PubMed 15972725
- Jennifer L Fish, Yoichi Kosodo, Wolfgang Enard, Svante Pääbo, Wieland B Huttner Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc. Natl. Acad. Sci. U.S.A.: 2006, 103(27);10438-43 PubMed 16798874
- N E Faulkner, D L Dujardin, C Y Tai, K T Vaughan, C B O'Connell, Y Wang, R B Vallee A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nat. Cell Biol.: 2000, 2(11);784-91 PubMed 11056532
- Anthony Wynshaw-Boris, Tiziano Pramparo, Yong Ha Youn, Shinji Hirotsune Lissencephaly: mechanistic insights from animal models and potential therapeutic strategies. Semin. Cell Dev. Biol.: 2010, 21(8);823-30 PubMed 20688183
- Jessica Yingling, Yong Ha Youn, Dawn Darling, Kazuhito Toyo-Oka, Tiziano Pramparo, Shinji Hirotsune, Anthony Wynshaw-Boris Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division. Cell: 2008, 132(3);474-86 PubMed 18267077
- M Borrell-Pagès, D Zala, S Humbert, F Saudou Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell. Mol. Life Sci.: 2006, 63(22);2642-60 PubMed 17041811
- Sean J Morrison, Judith Kimble Asymmetric and symmetric stem-cell divisions in development and cancer. Nature: 2006, 441(7097);1068-74 PubMed 16810241
- Sandra S McAllister, Robert A Weinberg Tumor-host interactions: a far-reaching relationship. J. Clin. Oncol.: 2010, 28(26);4022-8 PubMed 20644094
- R Fodde, R Smits Disease model: familial adenomatous polyposis. Trends Mol Med: 2001, 7(8);369-73 PubMed 11516998
- David P Minde, Zeinab Anvarian, Stefan Gd Rüdiger, Madelon M Maurice Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? Mol. Cancer: 2011, 10;101 PubMed 21859464
- L K Su, M Burrell, D E Hill, J Gyuris, R Brent, R Wiltshire, J Trent, B Vogelstein, K W Kinzler APC binds to the novel protein EB1. Cancer Res.: 1995, 55(14);2972-7 PubMed 7606712
- K B Kaplan, A A Burds, J R Swedlow, S S Bekir, P K Sorger, I S Näthke A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat. Cell Biol.: 2001, 3(4);429-32 PubMed 11283619
- K B Kaplan, A A Burds, J R Swedlow, S S Bekir, P K Sorger, I S Näthke A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat. Cell Biol.: 2001, 3(4);429-32 PubMed 11283619
- Rebecca A Green, Kenneth B Kaplan Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J. Cell Biol.: 2003, 163(5);949-61 PubMed 14662741
- Anthony Tighe, Victoria L Johnson, Stephen S Taylor Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability. J. Cell. Sci.: 2004, 117(Pt 26);6339-53 PubMed 15561772
- Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G