198:, asymmetric cell division plays an important role in neural development. Neuroblasts are the progenitor cells which divide asymmetrically to give rise to another neuroblast and a ganglion mother cell (GMC). The neuroblast repeatedly undergoes this asymmetric cell division while the GMC continues on to produce a pair of neurons. Two proteins play an important role in setting up this cell fate asymmetry in the neuroblast, Prospero and Numb. These proteins are both synthesized in the neuroblast and segregate into only the GMC during divisions. Numb is a suppressor of Notch, therefore the asymmetric segregation of Numb to the basal cortex biases the response of the daughter cells to Notch signaling, resulting in two distinct cell fates. Prospero is required for gene regulation in GMCs. It is equally distributed throughout the neuroblast cytoplasm, but becomes localized at the basal cortex when the neuroblast starts to undergo mitosis. Once the GMC buds off from the basal cortex, Prospero becomes translocated into the GMC nucleus to act as a transcription factor.
347:
transcripts associated with other functions fail to exhibit such a localization. Moreover, disruption of microtubule polymerization with nocodazole, and of actin polymerization with cytochalisin B, shows the cytoskeleton is also important in this asymmetry. It appears that microtubules are not required to recruit the mRNA to the centrosome, and that actin is required to attach the centrosome to the cortex. Finally, introducing multiple centrosomes into one cell by inhibiting cytokinesis shows that mRNA dependably localizes on the correct centrosome, suggesting intrinsic differences between each centrosomal composition. It is important to note that these results reflect experiments performed after the first two divisions, yet still demonstrate a different molecular means of establishing asymmetry in a dividing cell.
111:
299:. Embryos inherit a single centrosome which localizes in the prospective larger CD cell cytoplasm and emits radial microtubules during anaphase that contribute to both the mitotic spindle as well as cortical asters. However, the microtubule organizing center of the prospective smaller AB cell emits only microtubules that commit to the mitotic spindle and not cortical bound asters. When embryos are compressed or deformed, asymmetric spindles still form, and staining for gamma tubulin reveals that the second microtubule organizing center lacks the molecular signature of a centrosome. Furthermore, when centrosome number is doubled,
222:. In other words, the loss of apical cortical myosin allows hydrostatic pressure to push against the apical cell membrane, increasing the size of the apical region that is bound to become the larger neuroblast after cell division. Generation of apical and basal myosin flows simultaneously results in symmetric cell division, and delaying of basal myosin flows prevents normal expansion of the basal region of the dividing cell. Although this mechanism is spindle-independent, the spindle is important for setting up the cleavage furrow position, for bringing myosin to the cleavage furrow, and for driving basal myosin clearing.
320:, but relies on a modified mechanism. Compression experiments on the robusta embryo do not affect asymmetric division, suggesting the mechanism, like tubifex, uses a cortical independent molecular pathway. In robusta, antibody staining reveals that the mitotic spindle forms symmetrically until metaphase and stems from two biastral centrosomes. At the onset of metaphase, asymmetry becomes apparent as the centrosome of the prospective larger CD cell lengthens cortical asters while the asters of the prospective smaller AB cell become downregulated. Experiments using
368:), and another that maybe of the same potency or stimulated to further differentiate into specialized cell types such as neurons. This stimulated differentiation arises from many factors which can be divided into two broad categories: intrinsic and extrinsic. Intrinsic factors generally involve differing amounts of cell-fate determinants being distributed into each daughter cell. Extrinsic factors involve interactions with neighboring cells and the micro and macro environment of the precursor cell.
218:, resulting in the timely loss of myosin and Rok from the apical cortex at anaphase onset. The apical myosin flows basally to where the cleavage furrow is positioned. Subsequently, the proteins Tum and Pav at the central spindle recruit myosin to increase myosin concentration, generating a myosin gradient to drive apical myosin flow from the basal cortex. This spatiotemporal control of myosin localization results in the asymmetric loss of cortical tension that normally pushes against
275:
171:
The alignment of the spindle is mediated by the PAR proteins, which regulate the positioning of the centrosomes along the A/P axis as well as the movement of the mitotic spindle along the A/P axis. Following this first asymmetric division, the AB daughter cell divides symmetrically, giving rise to ABa and ABp, while the P1 daughter cell undergoes another asymmetric cell division to produce P2 and EMS. This division is also dependent on the distribution of the PAR proteins.
112:
113:
115:
167:(partitioning defective), which are a conserved group of proteins that function in establishing cell polarity during development. These proteins are initially distributed uniformly throughout the zygote and then become polarized with the creation of the posterior pole. This series of events allows the single celled zygote to obtain polarity through an unequal distribution of multiple factors.
184:
329:
forced symmetric division in a significant number of embryos. Treatment with either drug at these concentrations fails to disrupt normal centrosome dynamics, suggesting that a balance of microtubule polymerization and depolymerization represents another mechanism for establishing asymmetric cell division in spilarian development.
190:(blue) is asymmetrically distributed within the neuroblast. Following cell division, the GMC contains the Numb protein which suppresses Notch signaling. The other daughter cell is receptive to Notch signaling, causing distinct cellular responses, and ultimately two distinct cell fates between the daughter cells.
206:
Without the presence of
Inscuteable, the positioning of the mitotic spindle and the cell fate determinants in relationship to each other becomes randomized. Inscuteable mutants display a uniform distribution of Miranda and Numb at the cortex, and the resulting daughter cells display identical neuronal fates.
201:
Other proteins present in the neuroblast mediate the asymmetric localization of Numb and
Prospero. Miranda is an anchoring protein that binds to Prospero and keeps it in the basal cortex. Following the generation of the GMC, Miranda releases Prospero and then becomes degraded. The segregation of Numb
225:
Actomyosin-based cortical flows direct a reorganization of the plasma membrane and cell cortex of the neuroblast, which is needed to generate the size difference between daughter cells. Early in mitosis, cortical flows collect membrane folds and protrusions around the apical pole forming a polarized
209:
In addition to the two daughter cells having separate fates, they have different cell sizes; the resulting neuroblast is much larger than the GMC. However, unlike with the proper segregation of fate determinants, asymmetric cell division that gives rise to cell size asymmetry is spindle-independent.
170:
The single cell is now set up to undergo an asymmetric cell division, however the orientation in which the division occurs is also an important factor. The mitotic spindle must be oriented correctly to ensure that the proper cell fate determinants are distributed appropriately to the daughter cells.
278:
Asymmetric cell division is integral during development. In spiralia, the first cleavage can be either symmetric or asymmetric, as shown in the left panel. Asymmetry can be accomplished through simple unequal segregation of cell fate determinants across a single plane, through sequestration of cell
35:
divide asymmetrically to give rise to two distinct daughter cells: one copy of the original stem cell as well as a second daughter programmed to differentiate into a non-stem cell fate. (In times of growth or regeneration, stem cells can also divide symmetrically, to produce two identical copies of
205:
The mitotic spindle must also align parallel to the asymmetrically distributed cell fate determinants to allow them to become segregated into one daughter cell and not the other. The mitotic spindle orientation is mediated by
Inscuteable, which is segregated to the apical cortex of the neuroblast.
44:
between the cells, from surrounding cells, or from the precursor cell. This mechanism is known as extrinsic asymmetric cell division. In the second mechanism, the prospective daughter cells are inherently different at the time of division of the mother cell. Because this latter mechanism does not
162:
flux resulting in the movement of the pronucleus and centrosomes towards one pole. The centrosomes deposited by the sperm are responsible for the establishment of the posterior pole within the zygote. Sperm with mutant or absent centrosomes fail to establish a posterior pole. The establishment of
328:
support this observation. Taxol, which stabilized microtubules, forced a significant number of embryos to cleave symmetrically when used at a moderate concentration. Moreover, embryos treated with nocodazole, which sequesters tubulin dimers and promotes microtubule depolymerization, similarly
420:
contain rare subpopulation of cancer stem cells which are capable to divide asymmetrically. The asymmetric division in these cells is regulated by cancer niche (microenvironment) and Wnt pathway. Blocking the Wnt pathway with IWP2 (WNT antagonist) or siRNA-TCF4 resulted in high suppression of
346:
experiments show that mRNA transcripts co-localize with centrosomes during early cleavage. Consequently, these transcripts are inherited in a stereotypical fashion to distinct cells. All mRNA transcripts followed have been implicated in body axis patterning, and in situ hybridization for
279:
fate determinants in a polar lobe which is absorbed by one of the daughter cells, or a combination of both processes. The right panel summarizes the mechanisms of spiralian asymmetric cleavage discussed here. Red features indicate the molecule(s) implicated in establishing asymmetry.
114:
226:
membrane reservoir. As myosin clears from the apical cortex and cleavage furrow ingression causes hydrostatic pressure to increase, the stores of membrane within the reservoir are used to expand the apical region which becomes the larger daughter cell after division.
371:
In addition to the aforementioned
Drosophila neuronal example, it was proposed that the macrosensory organs of the Drosophila, specifically the glial cells, also arise from a similar set of asymmetric division from a single progenitor cell via regulation of the
404:, and could therefore constitute an early step in the tumorogenic transformation of stem and progenitor cells. In normal non-tumor stem cells, a number of genes have been described which are responsible for pluripotency, such as
290:
has been shown to demonstrate an interesting asymmetric cell division at the point of first embryonic cleavage. Unlike the classic idea of cortical differences at the zygotic membrane that determine spindle asymmetry in the
384:. In this manner, the daughter cell is forced to interact with the heavily sulfated molecules, which stimulate it to differentiate while the other daughter cell remains in the original niche in a quiescent state.
428:
in asymmetric cell divisions which are involved in tumor growth are loss-of-function mutations. The first suggestion that loss of asymmetric cell division might be involved in tumorigenesis came from studies of
437:
in situ. In these mutants cells divide more symmetrically and generate mis-specified progeny that fail to exit the cell cycle and differentiate, but rather proliferate continuously and form a tumor cell mass.
380:. An example of how extrinsic factors bring about this phenomenon is the physical displacement of one of the daughter cells out of the original stem cell niche, exposing it to signalling molecules such as
39:
In principle, there are two mechanisms by which distinct properties may be conferred on the daughters of a dividing cell. In one, the daughter cells are initially equivalent but a difference is induced by
416:. These genes have been discovered also in the case of cancer stem cells, and shows that their aberrant expression is essential for the formation of tumor cell mass. For example, it has been shown that
261:), research into the processes that govern spiralian development is comparatively lacking. However, one unifying feature shared among spiralia is the pattern of cleavage in the early embryo known as
214:
and its upstream components. Apical localization of Pins (Partner of
Inscuteable) by Inscuteable allows Pins-dependent apical Protein Kinase N (Pkn) localization during metaphase. Pkn inhibits
364:
undergoes many cell divisions that give rise to various cell types, including embryonic stem cells. Asymmetric divisions of these embryonic cells gives rise to one cell of the same potency (
773:
Sadler PL, Shakes DC (January 2000). "Anucleate
Caenorhabditis elegans sperm can crawl, fertilize oocytes and direct anterior-posterior polarization of the 1-cell embryo".
130:, a series of asymmetric cell divisions in the early embryo are critical in setting up the anterior/posterior, dorsal/ventral, and left/right axes of the body plan. After
1889:
Gho M, Bellaïche Y, Schweisguth F (August 1999). "Revisiting the
Drosophila microchaete lineage: a novel intrinsically asymmetric cell division generates a glial cell".
985:
Ikeshima-Kataoka H, Skeath JB, Nabeshima Y, Doe CQ, Matsuzaki F (December 1997). "Miranda directs
Prospero to a daughter cell during Drosophila asymmetric divisions".
433:. Studies of loss-of-function mutations in key regulators of asymmetric cell division including lgl, aurA, polo, numb and brat, revealed hyperproliferative
332:
Ilyanasa obsoleta: A third, less traditional mechanism contributing to asymmetric cell division in spiralian development has been discovered in the mollusk
334:
693:"The spd-2 gene is required for polarization of the anteroposterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote"
365:
1257:"Cell Polarity Regulates Biased Myosin Activity and Dynamics during Asymmetric Cell Division via Drosophila Rho Kinase and Protein Kinase N"
1424:"Consumption of a polarized membrane reservoir drives asymmetric membrane expansion during the unequal divisions of neural stem cells"
640:
Cowan CR, Hyman AA (September 2004). "Centrosomes direct cell polarity independently of microtubule assembly in C. elegans embryos".
241:) represent a diverse clade of animals whose species comprise the bulk of the bilaterian animals present today. Examples include
2128:
1658:
734:"Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains"
202:
is mediated by Pon (the partner of Numb protein). Pon binds to Numb and colocalizes with it during neuroblast cell division.
1787:
Lambert JD, Nagy LM (December 2002). "Asymmetric inheritance of centrosomally localized mRNAs during embryonic cleavages".
2024:"Wnt and the cancer niche: paracrine interactions with gastrointestinal cancer cells undergoing asymmetric cell division"
1307:"Spatio-temporally separated cortical flows and spindle geometry establish physical asymmetry in fly neural stem cells"
303:
embryos cleave symmetrically, suggesting this monoastral mechanism of asymmetric cell division is centrosome dependent.
46:
1745:"Asymmetrization of first cleavage by transient disassembly of one spindle pole aster in the leech Helobdella robusta"
2071:
Gonzalez C (June 2007). "Spindle orientation, asymmetric division and tumour suppression in
Drosophila stem cells".
1926:"Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells"
901:
Matsuzaki F (February 2000). "Asymmetric division of
Drosophila neural stem cells: a basis for neural diversity".
2148:
2123:. Progress in Molecular and Subcellular Biology. Vol. 45. Berlin, Heidelberg, New York: Springer Verlag.
1045:"Spatiotemporally Controlled Myosin Relocalization and Internal Pressure Generate Sibling Cell Size Asymmetry"
455:
Morrison SJ, Kimble J (June 2006). "Asymmetric and symmetric stem-cell divisions in development and cancer".
215:
857:
Schneider SQ, Bowerman B (2003). "Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote".
400:
exit and differentiation. Disruption of asymmetric cell division leads to aberrant self-renewal and impairs
810:"C. elegans PAR proteins function by mobilizing and stabilizing asymmetrically localized protein complexes"
163:
this polarity initiates the polarized distribution of a group of proteins present in the zygote called the
605:
Goldstein B, Hird SN (May 1996). "Specification of the anteroposterior axis in Caenorhabditis elegans".
138:
to allow for the first asymmetric cell division. This first division produces two distinctly different
1476:"Actin-dependent membrane polarization reveals the mechanical nature of the neuroblast polarity cycle"
1680:
51:
asymmetry. The term asymmetric cell division usually refers to such intrinsic asymmetric divisions.
401:
253:. Although much is known at the cellular and molecular level about the other bilateralian clades (
1305:
Roubinet C, Tsankova A, Pham TT, Monnard A, Caussinus E, Affolter M, Cabernard C (November 2017).
1363:
417:
413:
373:
90:
1584:"Asymmetric recruitment and actin-dependent cortical flows drive the neuroblast polarity cycle"
84:
1697:
Shimizu T, Ishii R, Takahashi H (June 1998). "Unequal cleavage in the early Tubifex embryo".
409:
377:
339:
45:
depend on interactions of cells with each other or with their environment, it must rely on
1847:
1796:
1375:
1318:
1113:
1056:
994:
870:
821:
649:
464:
946:"Control of daughter cell fates during asymmetric division: interaction of Numb and Notch"
8:
1364:"Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows"
1159:"Asymmetric cortical extension shifts cleavage furrow position in Drosophila neuroblasts"
381:
1851:
1800:
1641:
Henry JJ, Martindale MQ (1999). "Conservation and innovation in spiralian development".
1448:
1423:
1379:
1322:
1117:
1060:
998:
825:
653:
468:
2096:
2048:
2023:
1999:
1974:
1950:
1925:
1871:
1820:
1722:
1668:
1618:
1583:
1559:
1524:
1500:
1475:
1399:
1339:
1306:
1237:
1183:
1158:
1134:
1101:
1077:
1044:
1018:
926:
673:
582:
561:
498:
343:
308:
210:
The mechanism instead relies on the spatial and temporal organization of myosin on the
962:
945:
914:
750:
733:
183:
2124:
2088:
2053:
2004:
1975:"Asymmetric cell division of stem and progenitor cells during homeostasis and cancer"
1955:
1906:
1863:
1812:
1766:
1714:
1710:
1654:
1623:
1605:
1564:
1546:
1505:
1453:
1391:
1344:
1278:
1229:
1188:
1139:
1082:
1010:
967:
918:
874:
839:
790:
755:
714:
665:
622:
587:
539:
490:
262:
2100:
1726:
1241:
1043:
Pham TT, Monnard A, Helenius J, Lund E, Lee N, Müller DJ, Cabernard C (March 2019).
2080:
2043:
2035:
1994:
1986:
1945:
1937:
1898:
1875:
1855:
1824:
1804:
1756:
1706:
1646:
1613:
1595:
1554:
1536:
1495:
1487:
1443:
1435:
1403:
1383:
1334:
1326:
1268:
1219:
1178:
1170:
1129:
1121:
1072:
1064:
1022:
1002:
957:
910:
866:
829:
782:
745:
704:
677:
657:
614:
577:
569:
529:
480:
472:
930:
502:
1650:
1525:"Phases of cortical actomyosin dynamics coupled to the neuroblast polarity cycle"
1491:
1439:
1273:
1256:
286:
219:
64:
24:
1761:
1744:
1330:
1068:
238:
72:
41:
1990:
834:
809:
2142:
1609:
1550:
808:
Cheeks RJ, Canman JC, Gabriel WN, Meyer N, Strome S, Goldstein B (May 2004).
396:
cells, asymmetric cell division balances proliferation and self-renewal with
258:
131:
60:
28:
1941:
1902:
1174:
573:
2092:
2057:
2022:
Xin HW, Ambe CM, Ray S, Kim BK, Koizumi T, Wiegand GW, et al. (2013).
2008:
1959:
1910:
1816:
1770:
1627:
1568:
1509:
1457:
1395:
1348:
1282:
1233:
1192:
1143:
1086:
922:
878:
843:
794:
759:
718:
709:
692:
669:
618:
591:
534:
517:
494:
274:
246:
143:
68:
1867:
1718:
1014:
971:
786:
626:
543:
1157:
Connell M, Cabernard C, Ricketson D, Doe CQ, Prehoda KE (November 2011).
485:
211:
187:
119:
Asymmetric cell divisions during the first steps of the embryogenesis of
1808:
1600:
1541:
1387:
1125:
661:
476:
1224:
1207:
434:
430:
397:
393:
321:
296:
250:
155:
151:
139:
59:
In order for asymmetric division to take place the mother cell must be
164:
2039:
1924:
Hayes AJ, Tudor D, Nowell MA, Caterson B, Hughes CE (February 2008).
357:
254:
159:
32:
2084:
1362:
Mayer M, Depken M, Bois JS, Jülicher F, Grill SW (September 2010).
425:
234:
147:
95:
80:
1859:
1006:
984:
1255:
Tsankova A, Pham TT, Garcia DS, Otte F, Cabernard C (July 2017).
242:
312:
exhibits a similar asymmetry in the first embryonic division as
31:
which give rise to daughter cells of equivalent fates. Notably,
27:
with different cellular fates. This is in contrast to symmetric
732:
Hamill DR, Severson AF, Carter JC, Bowerman B (November 2002).
361:
135:
1643:
Reproductive Strategies and Developmental Patterns in Annelids
295:
embryo, the first cleavage in tubifex relies on the number of
16:
Production of two daughter cells with different cellular fates
405:
325:
76:
1156:
731:
1304:
1102:"A spindle-independent cleavage furrow positioning pathway"
562:"Asymmetric cell division and axis formation in the embryo"
1972:
1838:
Jan YN, Jan LY (April 1998). "Asymmetric cell division".
690:
1923:
807:
1973:
Gómez-López S, Lerner RG, Petritsch C (February 2014).
1888:
1361:
1208:"Drosophila neuroblasts: a model for stem cell biology"
1042:
1254:
1696:
896:
894:
892:
890:
888:
1099:
174:
1100:Cabernard C, Prehoda KE, Doe CQ (September 2010).
885:
1582:Oon, Chet Huan; Prehoda, Kenneth E (2019-05-08).
1523:Oon, Chet Huan; Prehoda, Kenneth E (2021-11-15).
1422:LaFoya, Bryce; Prehoda, Kenneth E. (April 2023).
856:
356:Animals are made up of a vast number of distinct
2140:
691:O'Connell KF, Maxwell KN, White JG (June 2000).
351:
2118:
1930:The Journal of Histochemistry and Cytochemistry
1640:
1474:LaFoya, Bryce; Prehoda, Kenneth E. (May 2021).
71:of these events has been most studied in three
67:must be aligned with the axis of polarity. The
515:
454:
2021:
1473:
1421:
1205:
604:
555:
553:
158:are deposited within the egg, which causes a
1882:
772:
101:
1786:
1742:
229:
94:. A later focus has been on development in
1782:
1780:
1692:
1690:
1581:
1522:
639:
598:
559:
550:
2047:
1998:
1949:
1760:
1699:Development, Growth & Differentiation
1617:
1599:
1558:
1540:
1499:
1447:
1338:
1272:
1223:
1182:
1133:
1076:
961:
943:
900:
833:
749:
708:
581:
533:
484:
448:
2070:
273:
182:
109:
1777:
1687:
1206:Homem CC, Knoblich JA (December 2012).
518:"Asymmetric cell division: from A to Z"
2141:
1837:
1738:
1736:
871:10.1146/annurev.genet.37.110801.142443
516:Hawkins N, Garriga G (December 1998).
134:, events are already occurring in the
54:
1634:
1469:
1467:
1417:
1415:
1413:
1300:
1298:
1296:
1294:
1292:
1038:
1036:
1034:
1032:
1979:Cellular and Molecular Life Sciences
1733:
944:Guo M, Jan LY, Jan YN (July 1996).
13:
2111:
1645:. Vol. 402. pp. 255–65.
1464:
1410:
1289:
1029:
560:Gönczy P, Rose LS (October 2005).
387:
14:
2160:
1743:Ren X, Weisblat DA (April 2006).
284:Tubifex tubifex: The sludge worm
269:Mechanisms of asymmetric division
1711:10.1046/j.1440-169x.1998.00001.x
2119:Macieira-Coelho A, ed. (2007).
2064:
2015:
1966:
1917:
1831:
1575:
1516:
1355:
1248:
1199:
1150:
1093:
978:
937:
903:Current Opinion in Neurobiology
850:
801:
766:
725:
684:
633:
509:
306:Helobdella robusta: The leech
1:
1163:Molecular Biology of the Cell
963:10.1016/s0896-6273(00)80278-0
915:10.1016/s0959-4388(99)00052-5
751:10.1016/s1534-5807(02)00327-1
441:
352:In stem cells and progenitors
142:, termed AB and P1. When the
1651:10.1007/978-94-017-2887-4_15
1492:10.1016/j.celrep.2021.109146
1440:10.1016/j.devcel.2023.04.006
1274:10.1016/j.devcel.2017.06.012
7:
1762:10.1016/j.ydbio.2005.12.049
271:(See Figure, right panel):
10:
2165:
1331:10.1038/s41467-017-01391-w
1069:10.1016/j.isci.2019.02.002
421:asymmetric cell division.
360:. During development, the
237:(commonly synonymous with
1991:10.1007/s00018-013-1386-1
859:Annual Review of Genetics
835:10.1016/j.cub.2004.05.022
2121:Asymmetric Cell Division
2073:Nature Reviews. Genetics
418:gastrointestinal cancers
230:In spiralian development
21:asymmetric cell division
1942:10.1369/jhc.7a7320.2007
1903:10.1242/dev.126.16.3573
1175:10.1091/mbc.e11-02-0173
574:10.1895/wormbook.1.30.1
522:Genes & Development
374:Notch signaling pathway
196:Drosophila melanogaster
91:Drosophila melanogaster
710:10.1006/dbio.2000.9714
619:10.1242/dev.122.5.1467
535:10.1101/gad.12.23.3625
280:
191:
123:
85:Caenorhabditis elegans
23:produces two daughter
2149:Developmental biology
1749:Developmental Biology
1311:Nature Communications
787:10.1242/dev.127.2.355
697:Developmental Biology
378:transcription factors
340:In situ hybridization
277:
186:
118:
220:hydrostatic pressure
36:the original cell.)
1852:1998Natur.392..775J
1809:10.1038/nature01241
1801:2002Natur.420..682L
1601:10.7554/eLife.45815
1542:10.7554/eLife.66574
1434:(11): 993–1003.e3.
1388:10.1038/nature09376
1380:2010Natur.467..617M
1323:2017NatCo...8.1383R
1126:10.1038/nature09334
1118:2010Natur.467...91C
1061:2019iSci...13....9P
999:1997Natur.390..625I
826:2004CBio...14..851C
662:10.1038/nature02825
654:2004Natur.431...92C
477:10.1038/nature04956
469:2006Natur.441.1068M
463:(7097): 1068–1074.
392:In normal stem and
382:chondroitin sulfate
88:, and the fruit fly
55:Intrinsic asymmetry
1428:Developmental Cell
1261:Developmental Cell
1225:10.1242/dev.080515
738:Developmental Cell
344:immunofluorescence
309:Helobdella robusta
281:
192:
179:neural development
124:
2130:978-3-540-69160-0
2028:Journal of Cancer
1846:(6678): 775–778.
1795:(6916): 682–686.
1660:978-90-481-5340-4
1374:(7315): 617–621.
1267:(2): 143–155.e5.
1218:(23): 4297–4310.
1169:(22): 4220–4226.
993:(6660): 625–629.
528:(23): 3625–3638.
335:Ilyanasa obsoleta
116:
2156:
2134:
2105:
2104:
2068:
2062:
2061:
2051:
2040:10.7150/jca.6896
2019:
2013:
2012:
2002:
1970:
1964:
1963:
1953:
1921:
1915:
1914:
1886:
1880:
1879:
1835:
1829:
1828:
1784:
1775:
1774:
1764:
1740:
1731:
1730:
1694:
1685:
1684:
1678:
1674:
1672:
1664:
1638:
1632:
1631:
1621:
1603:
1579:
1573:
1572:
1562:
1544:
1520:
1514:
1513:
1503:
1471:
1462:
1461:
1451:
1419:
1408:
1407:
1359:
1353:
1352:
1342:
1302:
1287:
1286:
1276:
1252:
1246:
1245:
1227:
1203:
1197:
1196:
1186:
1154:
1148:
1147:
1137:
1097:
1091:
1090:
1080:
1040:
1027:
1026:
982:
976:
975:
965:
941:
935:
934:
898:
883:
882:
854:
848:
847:
837:
805:
799:
798:
770:
764:
763:
753:
729:
723:
722:
712:
688:
682:
681:
637:
631:
630:
602:
596:
595:
585:
557:
548:
547:
537:
513:
507:
506:
488:
452:
216:Rho-kinase (Rok)
117:
2164:
2163:
2159:
2158:
2157:
2155:
2154:
2153:
2139:
2138:
2137:
2131:
2114:
2112:Further reading
2109:
2108:
2085:10.1038/nrg2103
2069:
2065:
2020:
2016:
1971:
1967:
1922:
1918:
1897:(16): 3573–84.
1887:
1883:
1836:
1832:
1785:
1778:
1741:
1734:
1695:
1688:
1676:
1675:
1666:
1665:
1661:
1639:
1635:
1580:
1576:
1521:
1517:
1472:
1465:
1420:
1411:
1360:
1356:
1303:
1290:
1253:
1249:
1204:
1200:
1155:
1151:
1112:(7311): 91–94.
1098:
1094:
1041:
1030:
983:
979:
942:
938:
899:
886:
855:
851:
820:(10): 851–862.
814:Current Biology
806:
802:
771:
767:
730:
726:
689:
685:
648:(7004): 92–96.
638:
634:
603:
599:
558:
551:
514:
510:
453:
449:
444:
402:differentiation
390:
388:Role in disease
354:
287:Tubifex tubifex
263:spiral cleavage
232:
181:
146:fertilizes the
110:
108:
65:mitotic spindle
57:
17:
12:
11:
5:
2162:
2152:
2151:
2136:
2135:
2129:
2115:
2113:
2110:
2107:
2106:
2079:(6): 462–472.
2063:
2034:(6): 447–457.
2014:
1985:(4): 575–597.
1965:
1936:(2): 125–138.
1916:
1881:
1830:
1776:
1755:(1): 103–115.
1732:
1705:(3): 257–266.
1686:
1677:|journal=
1659:
1633:
1574:
1515:
1463:
1409:
1354:
1288:
1247:
1198:
1149:
1092:
1028:
977:
936:
884:
849:
800:
781:(2): 355–366.
765:
744:(5): 673–684.
724:
683:
632:
613:(5): 1467–74.
597:
549:
508:
446:
445:
443:
440:
389:
386:
353:
350:
349:
348:
330:
304:
239:lophotrochozoa
231:
228:
180:
173:
107:
100:
56:
53:
29:cell divisions
15:
9:
6:
4:
3:
2:
2161:
2150:
2147:
2146:
2144:
2132:
2126:
2122:
2117:
2116:
2102:
2098:
2094:
2090:
2086:
2082:
2078:
2074:
2067:
2059:
2055:
2050:
2045:
2041:
2037:
2033:
2029:
2025:
2018:
2010:
2006:
2001:
1996:
1992:
1988:
1984:
1980:
1976:
1969:
1961:
1957:
1952:
1947:
1943:
1939:
1935:
1931:
1927:
1920:
1912:
1908:
1904:
1900:
1896:
1892:
1885:
1877:
1873:
1869:
1865:
1861:
1860:10.1038/33854
1857:
1853:
1849:
1845:
1841:
1834:
1826:
1822:
1818:
1814:
1810:
1806:
1802:
1798:
1794:
1790:
1783:
1781:
1772:
1768:
1763:
1758:
1754:
1750:
1746:
1739:
1737:
1728:
1724:
1720:
1716:
1712:
1708:
1704:
1700:
1693:
1691:
1682:
1670:
1662:
1656:
1652:
1648:
1644:
1637:
1629:
1625:
1620:
1615:
1611:
1607:
1602:
1597:
1593:
1589:
1585:
1578:
1570:
1566:
1561:
1556:
1552:
1548:
1543:
1538:
1534:
1530:
1526:
1519:
1511:
1507:
1502:
1497:
1493:
1489:
1486:(7): 109146.
1485:
1481:
1477:
1470:
1468:
1459:
1455:
1450:
1445:
1441:
1437:
1433:
1429:
1425:
1418:
1416:
1414:
1405:
1401:
1397:
1393:
1389:
1385:
1381:
1377:
1373:
1369:
1365:
1358:
1350:
1346:
1341:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1308:
1301:
1299:
1297:
1295:
1293:
1284:
1280:
1275:
1270:
1266:
1262:
1258:
1251:
1243:
1239:
1235:
1231:
1226:
1221:
1217:
1213:
1209:
1202:
1194:
1190:
1185:
1180:
1176:
1172:
1168:
1164:
1160:
1153:
1145:
1141:
1136:
1131:
1127:
1123:
1119:
1115:
1111:
1107:
1103:
1096:
1088:
1084:
1079:
1074:
1070:
1066:
1062:
1058:
1054:
1050:
1046:
1039:
1037:
1035:
1033:
1024:
1020:
1016:
1012:
1008:
1007:10.1038/37641
1004:
1000:
996:
992:
988:
981:
973:
969:
964:
959:
955:
951:
947:
940:
932:
928:
924:
920:
916:
912:
908:
904:
897:
895:
893:
891:
889:
880:
876:
872:
868:
864:
860:
853:
845:
841:
836:
831:
827:
823:
819:
815:
811:
804:
796:
792:
788:
784:
780:
776:
769:
761:
757:
752:
747:
743:
739:
735:
728:
720:
716:
711:
706:
702:
698:
694:
687:
679:
675:
671:
667:
663:
659:
655:
651:
647:
643:
636:
628:
624:
620:
616:
612:
608:
601:
593:
589:
584:
579:
575:
571:
567:
563:
556:
554:
545:
541:
536:
531:
527:
523:
519:
512:
504:
500:
496:
492:
487:
486:2027.42/62868
482:
478:
474:
470:
466:
462:
458:
451:
447:
439:
436:
432:
427:
422:
419:
415:
411:
407:
403:
399:
395:
385:
383:
379:
375:
369:
367:
363:
359:
345:
341:
337:
336:
331:
327:
323:
319:
315:
311:
310:
305:
302:
298:
294:
289:
288:
283:
282:
276:
272:
270:
266:
264:
260:
259:deuterostomia
256:
252:
248:
247:annelid worms
244:
240:
236:
227:
223:
221:
217:
213:
207:
203:
199:
197:
189:
185:
178:
172:
168:
166:
161:
157:
153:
149:
145:
141:
137:
133:
132:fertilization
129:
122:
105:
99:
97:
93:
92:
87:
86:
82:
78:
74:
73:animal models
70:
66:
62:
52:
50:
49:
43:
37:
34:
30:
26:
22:
2120:
2076:
2072:
2066:
2031:
2027:
2017:
1982:
1978:
1968:
1933:
1929:
1919:
1894:
1890:
1884:
1843:
1839:
1833:
1792:
1788:
1752:
1748:
1702:
1698:
1642:
1636:
1591:
1587:
1577:
1532:
1528:
1518:
1483:
1480:Cell Reports
1479:
1431:
1427:
1371:
1367:
1357:
1314:
1310:
1264:
1260:
1250:
1215:
1211:
1201:
1166:
1162:
1152:
1109:
1105:
1095:
1052:
1048:
990:
986:
980:
956:(1): 27–41.
953:
949:
939:
909:(1): 38–44.
906:
902:
862:
858:
852:
817:
813:
803:
778:
774:
768:
741:
737:
727:
703:(1): 55–70.
700:
696:
686:
645:
641:
635:
610:
606:
600:
565:
525:
521:
511:
460:
456:
450:
423:
391:
370:
366:self-renewal
355:
333:
317:
313:
307:
300:
292:
285:
268:
267:
233:
224:
208:
204:
200:
195:
193:
176:
169:
165:PAR proteins
150:, the sperm
127:
125:
120:
103:
89:
83:
69:cell biology
58:
47:
38:
20:
18:
1891:Development
1317:(1): 1383.
1212:Development
865:: 221–249.
775:Development
607:Development
297:centrosomes
212:cell cortex
160:cytoplasmic
156:centrosomes
140:blastomeres
106:development
1594:: e45815.
1535:: e66574.
442:References
435:phenotypes
431:Drosophila
398:cell-cycle
394:progenitor
358:cell types
322:nocodazole
314:C. elegans
293:C. elegans
251:entoprocta
249:, and the
177:Drosophila
152:pronucleus
144:sperm cell
128:C. elegans
121:C. elegans
104:C. elegans
63:, and the
33:stem cells
1679:ignored (
1669:cite book
1610:2050-084X
1551:2050-084X
255:ecdysozoa
61:polarized
48:intrinsic
42:signaling
2143:Category
2101:22558696
2093:17510666
2058:23901343
2009:23771628
1960:17938280
1911:10409503
1817:12478296
1771:16458880
1727:23026919
1628:31066675
1569:34779402
1510:34010656
1458:37116487
1449:10247545
1396:20852613
1349:29123099
1283:28712722
1242:14960710
1234:23132240
1193:21937716
1144:20811457
1087:30785031
1055:: 9–19.
1049:iScience
923:10679433
879:14616061
844:15186741
795:10603352
760:12431374
719:10885746
670:15343338
592:18050411
568:: 1–20.
566:WormBook
495:16810241
426:mutation
424:Another
243:mollusks
235:Spiralia
148:egg cell
96:spiralia
81:nematode
2049:3726705
2000:3901929
1951:2324172
1876:4392481
1868:9572136
1848:Bibcode
1825:4383189
1797:Bibcode
1719:9639353
1619:6524966
1560:8641948
1501:8174105
1404:4378520
1376:Bibcode
1340:5680339
1319:Bibcode
1184:3216648
1135:4028831
1114:Bibcode
1078:6383127
1057:Bibcode
1023:4423032
1015:9403694
995:Bibcode
972:8755476
822:Bibcode
678:4422297
650:Bibcode
627:8625834
583:4780927
544:9851969
465:Bibcode
318:tubifex
301:tubifex
2127:
2099:
2091:
2056:
2046:
2007:
1997:
1958:
1948:
1909:
1874:
1866:
1840:Nature
1823:
1815:
1789:Nature
1769:
1725:
1717:
1657:
1626:
1616:
1608:
1567:
1557:
1549:
1508:
1498:
1456:
1446:
1402:
1394:
1368:Nature
1347:
1337:
1281:
1240:
1232:
1191:
1181:
1142:
1132:
1106:Nature
1085:
1075:
1021:
1013:
987:Nature
970:
950:Neuron
931:187054
929:
921:
877:
842:
793:
758:
717:
676:
668:
642:Nature
625:
590:
580:
542:
503:715049
501:
493:
457:Nature
362:zygote
136:zygote
79:, the
75:: the
2097:S2CID
1872:S2CID
1821:S2CID
1723:S2CID
1588:eLife
1529:eLife
1400:S2CID
1238:S2CID
1019:S2CID
927:S2CID
674:S2CID
499:S2CID
414:Notch
406:Bmi-1
326:taxol
77:mouse
25:cells
2125:ISBN
2089:PMID
2054:PMID
2005:PMID
1956:PMID
1907:PMID
1864:PMID
1813:PMID
1767:PMID
1715:PMID
1681:help
1655:ISBN
1624:PMID
1606:ISSN
1565:PMID
1547:ISSN
1506:PMID
1454:PMID
1392:PMID
1345:PMID
1279:PMID
1230:PMID
1189:PMID
1140:PMID
1083:PMID
1011:PMID
968:PMID
919:PMID
875:PMID
840:PMID
791:PMID
756:PMID
715:PMID
666:PMID
623:PMID
588:PMID
540:PMID
491:PMID
412:and
376:and
342:and
324:and
316:and
257:and
188:Numb
154:and
2081:doi
2044:PMC
2036:doi
1995:PMC
1987:doi
1946:PMC
1938:doi
1899:doi
1895:126
1856:doi
1844:392
1805:doi
1793:420
1757:doi
1753:292
1707:doi
1647:doi
1614:PMC
1596:doi
1555:PMC
1537:doi
1496:PMC
1488:doi
1444:PMC
1436:doi
1384:doi
1372:467
1335:PMC
1327:doi
1269:doi
1220:doi
1216:139
1179:PMC
1171:doi
1130:PMC
1122:doi
1110:467
1073:PMC
1065:doi
1003:doi
991:390
958:doi
911:doi
867:doi
830:doi
783:doi
779:127
746:doi
705:doi
701:222
658:doi
646:431
615:doi
611:122
578:PMC
570:doi
530:doi
481:hdl
473:doi
461:441
410:Wnt
338:.
194:In
175:In
126:In
102:In
19:An
2145::
2095:.
2087:.
2075:.
2052:.
2042:.
2030:.
2026:.
2003:.
1993:.
1983:71
1981:.
1977:.
1954:.
1944:.
1934:56
1932:.
1928:.
1905:.
1893:.
1870:.
1862:.
1854:.
1842:.
1819:.
1811:.
1803:.
1791:.
1779:^
1765:.
1751:.
1747:.
1735:^
1721:.
1713:.
1703:40
1701:.
1689:^
1673::
1671:}}
1667:{{
1653:.
1622:.
1612:.
1604:.
1590:.
1586:.
1563:.
1553:.
1545:.
1533:10
1531:.
1527:.
1504:.
1494:.
1484:35
1482:.
1478:.
1466:^
1452:.
1442:.
1432:58
1430:.
1426:.
1412:^
1398:.
1390:.
1382:.
1370:.
1366:.
1343:.
1333:.
1325:.
1313:.
1309:.
1291:^
1277:.
1265:42
1263:.
1259:.
1236:.
1228:.
1214:.
1210:.
1187:.
1177:.
1167:22
1165:.
1161:.
1138:.
1128:.
1120:.
1108:.
1104:.
1081:.
1071:.
1063:.
1053:13
1051:.
1047:.
1031:^
1017:.
1009:.
1001:.
989:.
966:.
954:17
952:.
948:.
925:.
917:.
907:10
905:.
887:^
873:.
863:37
861:.
838:.
828:.
818:14
816:.
812:.
789:.
777:.
754:.
740:.
736:.
713:.
699:.
695:.
672:.
664:.
656:.
644:.
621:.
609:.
586:.
576:.
564:.
552:^
538:.
526:12
524:.
520:.
497:.
489:.
479:.
471:.
459:.
408:,
265:.
245:,
98:.
2133:.
2103:.
2083::
2077:8
2060:.
2038::
2032:4
2011:.
1989::
1962:.
1940::
1913:.
1901::
1878:.
1858::
1850::
1827:.
1807::
1799::
1773:.
1759::
1729:.
1709::
1683:)
1663:.
1649::
1630:.
1598::
1592:8
1571:.
1539::
1512:.
1490::
1460:.
1438::
1406:.
1386::
1378::
1351:.
1329::
1321::
1315:8
1285:.
1271::
1244:.
1222::
1195:.
1173::
1146:.
1124::
1116::
1089:.
1067::
1059::
1025:.
1005::
997::
974:.
960::
933:.
913::
881:.
869::
846:.
832::
824::
797:.
785::
762:.
748::
742:3
721:.
707::
680:.
660::
652::
629:.
617::
594:.
572::
546:.
532::
505:.
483::
475::
467::
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
