Journal of Cell Science o:10.1242/jcs.038083 doi: 4951–4961 125, Science Cell of Journal Peetades ainlIsiueo ilgclSine ejn,China Beijing, Science, Biological of Institute ` National address: *Present 2 1 Tang development Nan vertebrate in positioning Centrosome Commentary etradi hsclylne otences ihmicrotubules cell with the nucleus, the near to located linked physically as is is such 1997; and centrosome cells, center Mitchison, the nonpolarized and many fibroblasts, In (Desai interphase the 1999). motility Borisy, dictate and and Keating centrosomes polarity determining for shape, cells, important cell is which post-mitotic microtubules, of or organization interphase In and migration polarization cell in position Centrosome positioning. centrosome control that discuss in briefly mechanisms will molecular findings we some Finally, phase. exciting mitotic at the cells recent spindle in mitotic orientation the affects some affects position centrosome summarize centrosome phase. how mitotic understanding further the post or then of interphase at We position cells of the function and structure how discuss will role first We the development. vertebrate on during focus positioning two will that centrosome Commentary of locations This into types. non-random cell chromosomes between occupy differ Centrosomes replicated cells. separating daughter is which for the spindle, and a nucleus, responsible into and the grow of microtubules centrosome, ends reproduces each opposite from to 2011). centrosome move Stearns, centrosomes a and the two (Nigg Then as replicate centrosome cycle, acts each in centriole cell centrioles mother progression During the the cilia. mother primary cycle, through of the growth cell the termed centriole. for the site is daughter nucleation the pair from termed a exit is in Upon for younger centrioles the two microtubules. responsible whereas the nine-triplet centriole, of of are composed older is The that centriole Bornens, and Each proteins (Azimzadeh 2007). anchoring of and contains pair nucleation material a microtubule pericentriolar of which of cloud consists a 1A) (PCM), by (Fig. surrounded is cells that animal centrioles of centrosome The Introduction centrosome of roles vertebrates. in the organs discuss and reviewed studies tissues and The of in cues. systems, development words: these centrosomes the Key to developmental respond of to centrosome centrosomes vertebrate extend of of importance which functions examples on by composition the centrosome mechanisms review activities, and emphasis the that we revealed and structure these suggest Here, particular positioning have the here development. determine of a organ studies regarding that cues and means discovery with functional the tissue of By positioning, during positioning time, pace neurite decision spindle. same centriole or fate the mitotic and migration cell the years, and cell and formation the recent At as morphogenesis cilia In including such both accelerated. polarity, behaviors, orientation. controlling structures, continuously cell shape, spindle polarized cellular has mitotic cell regulating of as centrosomes regulating by well development in position animal as functions the during outgrowth, important roles as important has well have microtubules, centrosomes as of organizer transport major intracellular a centrosome, The Summary uhr o orsodne( correspondence for Authors eatetBohmsr n ipyis h nvriyo aiona a rnic,USA Francisco, USA San Francisco, California, San of California, University of The University Biophysics, The and Institute, Biochemistry Research Department Cardiovascular Anatomy, of Department 02 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2012. etooe eeomn,Mttcsideorientation spindle Mitotic Development, Centrosome, 1,2, * , ` n alc .Marshall F. Wallace and [email protected] [email protected] [email protected]; 2, ` ) nml,w osdrsvrleape fseilzdcl types cell specialized of examples below. several consider proteins we animals, PCM cell. entire the some a of has geometry depositing positioning the on centrosome and effect Thus, profound 2012). surface Priess, and apical (Feldman to cell moving (Mu centrosome domain the the with surface itself process, is specific centrosome-dependent array microtubule a apical–basal a an of to formation The vesicles 2004). ensure of might targeting axis endocytic polarity the and apical-basolateral The the secretory 2001). and along al., the apparatus MTs, et of (Rieder of 2B) the reorientation (Fig. array microtubule-based organization, cilium primary apical-basal microtubule a predominantly of assembly radial a of of formation loss apical by the Mu to 1984; accompanied move Keenan, centrioles and (Dylewski cells, surface epidermal cell and liver and duct to perpendicular 1982). Chentsov, oriented defined and be (Vorobjev have to substrate tend embryo also the centrioles kidney pig mother centrioles in the instance, For types, cells, axis. long cell their neighboring of deform that some orientations to forces enough In the strong that organelles. are suggesting centrosome the 1994), the cases, al., center nuclear et the some the of (Hulspas that In invagination close envelope an 2A). so within (Fig. resides is actually nucleus cortex centrosome and cell centrosome between the association to out radiating ta. 04.Teoinaino h troiir udeis bundle stereociliary which centriole, the the of of position orientation polarized (Frolenkov the surface The by apical stereocilia, 2004). predetermined the on al., called bundle et V-shape microvilli a sense form though cochlea) which mammalian the stimulation (in Corti of mechanical organ the in cells Hair Cochlea obte ovytevreyo etooepstosin positions centrosome of variety the convey better To intestinal airway, gland, mammary in cells epithelial most In sh 04,wihis which 2004), ¨sch, 4951 ¨sch, Journal of Cell Science eesn ocle yi rnlswti h immunological by the cells within infected granules destroy lytic (CTLs) so-called lymphocytes releasing T Cytotoxic exact cells the Immune Thus, unclear. 2007). movement remains nuclear outgrowth al., either axon or and et centrosomes between that (Umeshima of relationship movement demonstrated the centrosome with correlated cerebellum the always al., not mouse et is migration Xie developing nucleus cells 2007; granule al., of cultured migration et radial in Tsai of the imaging 2004; live drives al., However, 2003). et and it (Rivas Solecki that microtubules 1995; along suggesting Hatten, nucleus the nucleus, of the movement forward of ahead positioned 2010). in al., axonogenesis et distant (Distel However, occurs centrosome clearly 2005). the neurons from al., nuclei hindbrain et tegmental mouse Anda (de centrosome the formation of cultured inactivation adjacent whereas form in that 2005; centrosomes, axons two centrosomes al., two the of et in to number Anda results the cytokinesis de Doubling inhibiting 2005; by 1998). site al., Rivas, the et and determining (Bellion in Zmuda neurite role outgrowth the a to axon suggesting proximity of axon, close the in becomes found that often is centrosome The 2008). al., et also Neurons (Jones Corti bodies bundles. of basal organ the all stereociliary polarized of across alignment the cells uniform the of the that directing in functions likely al., morphology important become have is et and it (Frolenkov stereocilia Furthermore, orientation pattern determines positioning position, centriole symmetric the that appears round non-polarized it Therefore, a 2004). central, in relocated are distributed a centrioles the If cilium. to primary single a assembles pericentriolar PCM, and 1986). specific al., into et extends (Klotz material. which the rootlets matrix, of called side a structures proximal with striated The associated epithelium. is multiciliated body a basal from cell ( a 2007). in cell al., (centriole) anchoring the et contact for (Dawe that required fibers respectively transitional be cortex, forming to or thought centriole appendages the are distal at which microtubules and 1992), subdistal is al., the centriole et appendages, mother (Paintrand of The sets PCM. two by by orthogonally surrounded distinguished two are of that composed centrioles are oriented Centrosomes cells. vertebrate centrioles. most and centrosomes vertebrate of ( anatomy The 1. 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Verkhovsky cell al., 1991; for et Wakida are required 1984; centrosomes not al., keratocytes, types, and et cell leukocytes (Koonce some polymorphonuclear others in of in removal migration not or cell but ablation affect that to fact appears the centrosomes is migration centrosome cell between and connection position the complicating Further 1991). omto fteimn yas htmgthl xli a explain help might processes. both that in synapse centrosomes for immune in function shared the 2009), involved al., and of be ciliogenesis et between formation to (Finetti relationship in evolutionary synapse appear the an involved immunological suggesting also of the process Components centrioles, to motile 2D). trafficking onto (Fig. a cilia 2011) (Stinchcombe system, building al., granules Maly, the targets et transport lytic Tsun and to of intraflagellar their 2006; (Kim delivery moves al., the and pulling et centrosome directs cortical CTLs and The by 2009) between 2001). synapse al., formed immunological et is (Stinchcombe that synapse eidtencesi t el nwuddeihla sheets epithelial but wounded in 2002), cells al., PtK et in (Yvon nucleus cells the (CHO) behind and ovary 1984) the al., hamster of et ahead (Koonce Chinese (Yvon eosinophils located type in is cell migration centrosome during the the nucleus on example, depends For nucleus 2002). al., the centrosome et behind the or whether of However, the ahead edge. is between Golgi leading edge compartment the the recycling leading both and nucleus endocytic positions the the orientation often and and This complex 1981). centrosome nucleus al., the the et (Gotlieb between fibroblasts, oriented of becomes monolayers wounded migration In cell and healing Wound elc eilo aea elrarneet respectively. rearrangement, can cell centrosomes lateral positioned or lateral medial mesoderm of reflect or polarization polarized medial and of planar specifically, movements ectoderm the cells; This in become changes the gastrulation. reflect later might late of centrosomes and and planes mid mesoderm, the between and within ectoderm superficial-deep polarized the (Sepich a along through axes polarize first axis embryonic Centrosomes along 2011). mediolateral al., polarized et and highly is anteroposterior position of the centrosome of variety field the a zebrafish a gastrulation, to During of gastrulation. contributes including narrowing processes extension, morphogenetic dramatic and convergent lengthening a termed The cells, undergo shape. embryos in change vertebrate development, During extension Convergent II myosin of function a as vary can (Szabo activity nucleus and centrosome of Furthermore, direction 2010). 1994; the 1988). al., al., in et et point al., Katsumoto Schneider to 1977; et tend (Albrecht-Buehler, movement cells (Gudima cell migrating in migrating which in cilia over are centrioles primary surface regulated cell cells macrophages, the to also and the respect with lymphocytes vertically is oriented al., In are orientation et migrate cells. 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Box etooepsto n pnl retto r loregulated also are orientation spindle and position Centrosome system polarity intrinsic an is 2) Box (PCP, polarity cell Planar e ta. 05 h n cwigt,19) n zebrafish and 1998), Schweisguth, and Gho 2005; al., et pez as nw ssrbsu)and strabismus) as known (also Drosophila hs ee alit w rus which groups, two into fall genes These . ´ ae ta. 00 hw httePCP the that shows 2010) al., et galen fat dishevelled and dachsous Drosophila trynight starry , frizzled swl sa as well as , , prickle (Baena- (also , ih epn nld ohmlclradmcaia cues. mechanical and positioning molecular centrosome both which include (The to respond centrosome cues might the extrinsic the of Thus, position attachment 2006). the matrix dictate extracellular the can of in pattern Even shape orientation. the spindle (The cells, for interphase divisions used are cell that components of cortical orientation The 2007; the al., affect et also can tension uui yokltnaebt iasmld h daughter the disassembled, and actin both the if However, are 2000). al., cytoskeleton et fails (Piel cytoskeletons tubulin motion tubulin the or halt actin these the to in either and, is of centriole, centriole disruption mother daughter cases, the the Euteneuer than types, motile 1985; cell more Schliwa, some substantially In and 1992). Euteneuer the Schliwa, 2003; and both al., by 1990; et al., generation et Burakov (Buendia force cytoskeletons in active actin-based positioning and an microtubule- centrosome that involves reason, frame allow this systems for time many to (Rafelski Possibly cycle a 2011). cell slow within typical al., cue. a et too site during polarization this defined be cell allow to a would might at response motion capture in centrosome Brownian moved by how physically of Diffusion arises is question the centrosome present, is the cue polarity suitable a Once anchoring and generation Force eursteOF rti,ad nmc akn functional lacking mice in foot and, basal the protein, of (Chailley ODF2 Formation 2000). centrosome the al., the et requires of Hagiwara on 1989; orientation forces for al., during exert et point to body a focal cytoskeleton basal as microtubule a functions the the as it allow that a acts to suggesting in handle also tissues, beat foot ciliated 1991; in ciliary basal microtubules Sandoz, of The direction 1961). and the Gibbons, (Boisvieux-Ulrich in epithelium points multiciliated which 1B). body, (Fig. basal orientation which drive onto to force ‘handles’, exert or could points cytoskeleton could attachment the which as of and any serve distal rootlet, the potentially striated foot, the basal be and extends the small appendages, structures: the centriole subdistal fibrous out The thus, of pull centrosome. sets ripping main the might, to three of of positioning forces interactions instead for allows central way, Centriole–cytoskeleton that coherent core pieces. a structural in a centrosome the points that when suggesting is 2005), fragment attachment al., centriole et centrosomes (Abal stable them on centrioles, push microtubules mechanically Without required. centrosome, are the Panizzi 2007; on al., et 1988). Tamm, Pan in and 2010; 1990; Tamm al., also al., 2007; et but al., et Hirota surface et 2009; (Boisvieux-Ulrich cell al., cortex et the the Dawe of into out them only centrioles anchoring not the is, that propelling ciliogenesis stages, a during multiple Similarly, in at cortex 2009). potentially have cell actin, the also al., involves to also also et cells centrioles (Schmoranzer of microtubules these movement process the in that this (Gomes positioning in suggesting function important centrosome dynein, particularly but be involves 2005), to al., appears et actin in cortical microtubules of implicating microtubules further spindle 2010), Before movement. parallel. along al., centriole in move et centrioles on can (Jonsdottir act forces centrioles both that by suggesting cytokinesis, 2000), generated al., are et that (Piel moving stops centriole h aa ot(i.1)i oesae rtuinfo the from protrusion cone-shaped a is 1B) (Fig. foot basal The force exert to cytoskeleton tubulin and actin the for order In flow the healing, wound in re-positioning centrosome During ´ ye l,20)b otoln h ergto of segregation the controlling by 2005) al., et ry etooepstoig4957 positioning Centrosome ´ ye al., et ry ´ ry Journal of Cell Science pteilmsnhmltastos hsiseo how of question issue a and is processes This cell extracellular sheets influence of events epithelial migration subcellular transitions. of the as expansion epithelial–mesenchymal the such non-isotropic link tissues, of collectives, to developing large-scale the is of surveys with level challenge across behavior organelle organism-wide the major and at centrosomes second systematic, tissues of behavior A across for time. orientation developmental need and position clear centrosome animal a there Thus, mechanisms. in is it general making any centrosome cells, deduce to that of positioning difficult types extremely fact different between the centrosome widely by varies behavior hampered currently of is development understanding Our perspectives future and Conclusions processes. the developmental see for other to in interest required great proteins of such be is of will function It ninein 2009). mammalian al., developing Furthermore, et the (Wang requires ninein-mediatedneocortex in 2011). centrioles progenitors glia al., with radial for ninein maintaining (Matsumoto et of divisions (Ibi association role The ODF2 cell 2008). oriented a mammalian al., 2000). et in in suggesting al., morphogenesis anchoring tubular microtubule et cells, Mogensen for subdistal required endothelial 2005; the is al., of Ninein et component (Delgehyr microtubule-anchoring appendages a is centrioles in to ninein, cytoskeleton unknown. the remains linking TBCCD1 positioning protein of important centrosome Another role for mechanistic The crucial centriole (Gonc 2010). be al., cells mammalian et to in in healing shown wound later during positioning a was defects which a in and (TBCCD1), 2009), identified for I been Chlamydomonas containing screen has domain or that genetic cortex TBCC protein cell is centrosome-associated the cues onto 2007). polarity al., docking et (Dawe being proteins one ciliogenesis orientation, of likely recruitment rotational orientation, besides most functions ciliary the are additional appendages of subdistal for the foot, instead required basal the appendages, defective, epithelia unlike distal that is suggesting these multiciliated lacking itself al., subdistal are et in ciliogenesis centrioles of (Ishikawa cilium when formation primary foot but for single 2005), a required basal with is cells in 2012), the appendages al., required et is of al., which (Kunimoto et ODF2, assembly (Mogensen cells. be to multiciliated for pair appear of which centriole feet, specialization basal single lack a cells a these subdistal epithelial in only Centrioles in the 2000). function have similar epithelia, that a multiciliated have cells might in 1A) bodies (Fig. the appendages basal of for rest point the and rootlets the might cytoskeleton. between they 2003), interactions 2011). Glotzer, mediate al., and and et (Mishima actin dynamics Smith modulate can microtubule 2003; components rootlets spindle al., central striated Inner these et Because to protein, (Gromley relocate ciliogenesis kinesin-like centriolin) during mitotic opposite and Protein 1, protein, an as centromere cytokinesis (such in cytokinesis of to during cortex localize regulator midzone that the proteins spindle Interestingly, mitotic from foot. the basal away the to points direction which in resulting rootlet, 2012). oriented, al., et randomly (Kunimoto flow become cilia-driven bodies ineffective basal ODF2, 4958 nte addt o ikn etil retto ocell to orientation centriole linking for candidate Another attachment microtubule a as acting foot basal the to Similar striated the is body basal the to attached appendage other The ora fCl cec 2 (21) 125 Science Cell of Journal Flmne l,20;FlmnadMarshall, and Feldman 2007; al., et (Feldman ¸alves eghr . ilbun,J n onn,M. Bornens, and J. 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