Caenorhabditis elegans Embryo: Establishment of Asymmetry


In Caenorhabditis elegans, asymmetry is established in the one‐cell embryo in response to the position of the sperm provided centrosome. Asymmetric contraction of actin and myosin at the cortex leads to the localisation of the conserved PAR (partitioning defective) polarity proteins into anterior and posterior cortical domains. The PAR proteins and associated protein kinases generate cytoplasmic gradients of polarity mediators, which in turn regulate the anterior/posterior cytoplasmic localisation of downstream cell fate regulators. The PAR proteins also regulate a conserved G protein pathway that coordinates the division plane with the anterior/posterior axis. Thus, the first division is asymmetric and the daughter cells have different developmental fates. During the next few divisions, anterior/posterior asymmetries and cell–cell signalling events establish the dorsal/ventral and left–right axes of the embryo and further refine cell fates.

Key Concepts:

  • The C. elegans embryo exhibits an invariant pattern of asymmetric cell divisions that generates diverse cell types.

  • Asymmetric divisions are regulated by the conserved PAR proteins, which become localised in anterior and posterior cortical domains during polarity establishment after fertilisation.

  • Polarity establishment occurs in response to an unknown cue associated with the sperm centrosome, which causes an actomyosin cortical flow that localises the anterior PAR proteins.

  • PAR polarity cues create a cytoplasmic gradient of the polarity mediators MEX‐5 and MEX‐6, which act together with other polarity mediators to generate the asymmetric localisation of cell fate determinants.

  • Asymmetric localisation of cell fate determinants is accomplished mainly through protein degradation and translational regulation.

  • The localisation of cell fate determinants combined with cell–cell signalling events leads to specification of different developmental programmes in cells of the early embryo.

  • A conserved G protein pathway functions with the microtubule motor dynein to position the mitotic spindle on the polarity axis during asymmetric divisions.

Keywords: asymmetric division; polarity; PAR; actomyosin; spindle position; protein degradation; translational control

Figure 1.

Asymmetric cell divisions produce blastomeres with distinct fates. Posterior is to the right. (a–e) The invariant division pattern leads to a precise arrangement of cells and the birth of six founder cells. The names of the founder cells and the germ‐line precursor cells (P cells) are labelled, and cells derived from each founder are indicated by colour. (a) One‐cell. (b) Two‐cell. (c) Four‐cell. (d) Eight‐cell. (e) For simplicity, the 16‐cell embryo at bottom does not show the daughter cells of the fourth AB cleavage, which occurs at about the same time as the P3 division. (f) Diagrammatic representation of the early lineage, showing the major cell types produced by each founder cell. Horizontal lines indicate cell divisions, and the lengths of the vertical lines indicate relative differences in cell cycle rates of each blastomere.

Figure 2.

Establishment of polarity in the early embryo. Posterior is to the right in all embryos. (a) Just after fertilisation, PAR‐3/PAR‐6/PKC‐3 are initially localised uniformly at the cortex, and contractions (indentations) occur throughout the cortex. (b) The position of the male pronucleus and associated centrosomes results in a local cessation of cortical contractile activity at the closest cortical region, but cortical contractions continue in the anterior. (c) Cortical cytoplasm (curved arrows), NMY‐2 and anterior PARs begin to flow towards the anterior, and PAR‐2 and PAR‐1 localise to the posterior cortex. Internal cytoplasm flows towards the posterior (straight arrows). The posterior PAR domain expands as actomyosin contractions and PAR‐3/PAR‐6/PKC‐3 become localised to the anterior. (d) The female pronucleus migrates towards the sperm pronucleus as contraction culminates in a medial pseudocleavage furrow. (e) By the time of pronuclear meeting, P granules are enriched in the posterior half of the embryo. (f) First division is intrinsically asymmetric resulting in an anterior cell AB and a posterior cell P1 that differ in cytoplasmic inheritance and PAR protein domains. PAR‐2 and PAR‐1 are initially present around the entire P1 cortex, but as the cell cycle progresses, PAR protein asymmetry and cellular polarity are reestablished.

Figure 3.

Localisation of polarity mediators, cell fate determinants and signalling pathways in the early embryo. Colours are used to indicate the localisation of different proteins as indicated; the hatched nucleus indicates high levels of POP‐1 in addition to the other proteins; arrows show the direction of cell–cell signalling events. For simplicity, SKN‐1 and PAL‐1 are shown together in posterior nuclei. However, SKN‐1 levels decrease after the four‐cell stage. In contrast PAL‐1 is not present until the four‐cell stage and persists in 8–12 cell stage embryos after SKN‐1 disappears. Similarly, MEX‐5 and MEX‐3 are both enriched in the AB lineage. However, MEX‐5 is also present in an anterior/posterior gradient of each P cell by division and persists in the somatic daughter for several cycles, and MEX‐5 signal in the AB cells diminishes beginning at the four‐cell stage. MEX‐1, MEX‐3 and PIE‐1 are also present on P granules in the P cells.

Figure 4.

Division patterns are determined by centrosome migrations and nuclear rotation. All embryos are left views, except (g) which is a dorsal view. Posterior is to the right. The small green circles represent centrosomes, green lines represent astral microtubules and arrows indicate directions of centrosome movements. The number of astral microtubules drawn is reduced for clarity. Blue circles represent interphase or prophase nuclei, blue bars are chromosomes in metaphase or anaphase. (a) The female pronucleus meets the sperm pronucleus in the posterior. (b) The pronuclei centre and rotate so that the first spindle (c) is aligned on the long axis of the embryo. In two‐cell embryos (d), centrosomes migrate until they are on opposite sides of the nuclei. In P1, there is a subsequent 90° nuclear rotation (e) to align the spindle (f) on the anterior/posterior axis. At the four‐cell stage, centrosomes migrate onto the left/right axis (g) and the spindle forms on this axis in ABa and ABp (h, only the spindle pole is visible). In EMS, the nucleus then rotates 90° onto the anterior/posterior axis (h and i). A 45° nuclear rotation orients the P2 spindle towards the site of contact with EMS, but division is dorsal/ventral due to constraints of cellular arrangements and the eggshell (not shown).

Figure 5.

Model for PAR‐dependent spindle positioning. Gα/GPR signalling is required for forces that pull on microtubules from the cortex (+), whereas LET‐99 inhibits force (−). Note that LET‐99 and GPR/LIN‐5 localise to the entire cortex, but only the regions with highest levels are indicated for simplicity. (a) During nuclear rotation, GPR and LIN‐5 show a slight enrichment at the anterior cortex and LET‐99 localises to the cortex in a posterior band. Inhibition of GPR‐1/2 localisation in the band would result in reduced force on lateral‐posterior microtubules compared to the force acting on microtubules contacting the other regions of the cortex. As a result, the pronuclear centrosome complex would move anteriorly and rotate. (b) At metaphase/anaphase, GPR‐1/2 and LIN‐5 are highest at both poles and lowest in the LET‐99 region. The resulting asymmetry of forces acting on the posterior pole displaces the spindle. (c) Gα associates with LIN‐5 through the adaptor GPR. LIN‐5 is thought to recruit dynein. Anchored to the cortex through the Gα/GPR/LIN‐5 complex, dynein may supply force via cortical‐contacting astral microtubules. Additionally, microtubules almost immediately depolymerise on contacting the cortex, which may also assist in cortical force generation.



Afshar K, Werner ME, Tse YC, Glotzer M and Gonczy P (2010) Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH‐6 in one‐cell stage C. elegans embryos. Development 137: 237–247.

Beatty A, Morton D and Kemphues K (2010) The C. elegans homolog of Drosophila Lethal giant larvae functions redundantly with PAR‐2 to maintain polarity in the early embryo. Development 137: 3995–4004.

Betschinger J and Knoblich JA (2004) Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Current Biology 14: R674–R685.

Bienkowska D and Cowan CR (2012) Centrosomes can initiate a polarity axis from any position within one‐cell C. elegans embryos. Current Biology 22: 583–589.

Couwenbergs C, Labbe JC, Goulding M et al. (2007) Heterotrimeric G protein signaling functions with dynein to promote spindle positioning in C. elegans. Journal of Cell Biology 179: 15–22.

Cowan CR and Hyman AA (2007) Acto‐myosin reorganization and PAR polarity in C. elegans. Development 134: 1035–1043.

Daniels BR, Dobrowsky TM, Perkins EM, Sun SX and Wirtz D (2010) MEX‐5 enrichment in the C. elegans early embryo mediated by differential diffusion. Development 137: 2579–2585.

Evans TC and Hunter CP (2005). Translational control of maternal RNAs (10 November 2005), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.34.1,

Farley BM, Pagano JM and Ryder SP (2008) RNA target specificity of the embryonic cell fate determinant POS‐1. RNA 14: 2685–2697.

Fortin SM, Marshall SL, Jaeger EC et al. (2010) The PAM‐1 aminopeptidase regulates centrosome positioning to ensure anterior–posterior axis specification in one‐cell C. elegans embryos. Developmental Biology 344: 992–1000.

Galli M and van den Heuvel S (2008) Determination of the cleavage plane in early C. elegans embryos. Annual Review of Genetics 42: 389–411.

Galli M, Munoz J, Portegijs V et al. (2011) aPKC phosphorylates NuMA‐related LIN‐5 to position the mitotic spindle during asymmetric division. Nature Cell Biology 13: 1132–1138.

Gallo CM, Wang JT, Motegi F and Seydoux G (2010) Cytoplasmic partitioning of P granule components is not required to specify the germline in C. elegans. Science 330: 1685–1689.

Ghosh D and Seydoux G (2008) Inhibition of transcription by the Caenorhabditis elegans germline protein PIE‐1: genetic evidence for distinct mechanisms targeting initiation and elongation. Genetics 178: 235–243.

Goehring NW, Trong PK, Bois JS et al. (2011) Polarization of PAR proteins by advective triggering of a pattern‐forming system. Science 334: 1137–1141.

Gonczy P and Rose LS (2005) Asymmetric cell division and axis formation in the embryo (15 October 2005), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.30.1,

Griffin EE, Odde DJ and Seydoux G (2011) Regulation of the MEX‐5 gradient by a spatially segregated kinase/phosphatase cycle. Cell 146: 955–968.

Hao Y, Boyd L and Seydoux G (2006) Stabilization of cell polarity by the C. elegans RING protein PAR‐2. Developmental Cell 10: 199–208.

Hoege C, Constantinescu AT, Schwager A et al. (2010) LGL can partition the cortex of one‐cell Caenorhabditis elegans embryos into two domains. Current Biology 20: 1296–1303.

Jadhav S, Rana M and Subramaniam K (2008) Multiple maternal proteins coordinate to restrict the translation of C. elegans nanos‐2 to primordial germ cells. Development 135: 1803–1812.

Jenkins N, Saam JR and Mango SE (2006) CYK‐4/GAP provides a localized cue to initiate anteroposterior polarity upon fertilization. Science 313: 1298–1301.

Kemphues KJ and Strome S (1997) Fertilization and establishment of polarity in the embryo. In: Riddle DL, Blumenthal T, Meyer BJ and Priess JR (eds) C. elegans II, chap. 13, p. 335–359. NY: Cold Spring Harbor.

Krueger LE, Wu JC, Tsou MF and Rose LS (2010) LET‐99 inhibits lateral posterior pulling forces during asymmetric spindle elongation in C. elegans embryos. Journal of Cell Biology 189: 481–495.

Maduro MF (2006) Endomesoderm specification in Caenorhabditis elegans and other nematodes. Bioessays 28: 1010–1022.

Maduro MF (2010) Cell fate specification in the C. elegans embryo. Developmental Dynamics 239: 1315–1329.

Morin X and Bellaiche Y (2011) Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development. Developmental Cell 21: 102–119.

Motegi F and Sugimoto A (2006) Sequential functioning of the ECT‐2 RhoGEF, RHO‐1 and CDC‐42 establishes cell polarity in Caenorhabditis elegans embryos. Nature Cell Biology 8: 978–985.

Motegi F, Zonies S, Hao Y et al. (2011) Microtubules induce self‐organization of polarized PAR domains in Caenorhabditis elegans zygotes. Nature Cell Biology 13: 1361–1367.

Munro E and Bowerman B (2009) Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harbor Perspectives in Biology 1: a003400.

Nance J and Zallen JA (2011) Elaborating polarity: PAR proteins and the cytoskeleton. Development 138: 799–809.

Narbonne P, Hyenne V, Li S, Labbe JC and Roy R (2010) Differential requirements for STRAD in LKB1‐dependent functions in C. elegans. Development 137: 661–670.

Nguyen‐Ngoc T, Afshar K and Gonczy P (2007) Coupling of cortical dynein and G alpha proteins mediates spindle positioning in Caenorhabditis elegans. Nature Cell Biology 9: 1294–1302.

Ogura K, Kishimoto N, Mitani S, Gengyo‐Ando K and Kohara Y (2003) Translational control of maternal glp‐1 mRNA by POS‐1 and its interacting protein SPN‐4 in Caenorhabditis elegans. Development 130: 2495–2503.

Oldenbroek M, Robertson SM, Guven‐Ozkan T et al. (2012) Multiple RNA‐binding proteins function combinatorially to control the soma‐restricted expression pattern of the E3 ligase subunit ZIF‐1. Developmental Biology 363: 388–398.

Pagano JM, Farley BM, Essien KI and Ryder SP (2009) RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX‐3. Proceedings of the National Academy of Sciences of the USA 106: 20252–20257.

Pagano JM, Farley BM, McCoig LM and Ryder SP (2007) Molecular basis of RNA recognition by the embryonic polarity determinant MEX‐5. Journal of Biological Chemistry 282: 8883–8894.

Panbianco C, Weinkove D, Zanin E et al. (2008) A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning. Developmental Cell 15: 198–208.

Park DH and Rose LS (2008) Dynamic localization of LIN‐5 and GPR‐1/2 to cortical force generation domains during spindle positioning. Developmental Biology 315: 42–54.

Pohl C (2011) Left–right patterning in the C. elegans embryo: unique mechanisms and common principles. Communicative and Integrative Biology 4: 34–40.

Pohl C and Bao Z (2010) Chiral forces organize left‐right patterning in C. elegans by uncoupling midline and anteroposterior axis. Developmental Cell 19: 402–412.

Schnabel R and Priess JR (1997) Specification of cell fates in the early embryo. In: Riddle DL, Blumenthal T, Meyer BJ and Priess JR (eds) C. elegans II, chap. 14, p. 361–382. NY: Cold Spring Harbor.

Schneider SQ and Bowerman B (2003) Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote. Annual Review of Genetics 37: 221–249.

Schonegg S and Hyman AA (2006) CDC‐42 and RHO‐1 coordinate acto‐myosin contractility and PAR protein localization during polarity establishment in C. elegans embryos. Development 133: 3507–3516.

Tenlen JR, Molk JN, London N, Page BD and Priess JR (2008) MEX‐5 asymmetry in one‐cell C. elegans embryos requires PAR‐4‐ and PAR‐1‐dependent phosphorylation. Development 135: 3665–3675.

Tsai MC and Ahringer J (2007) Microtubules are involved in anterior–posterior axis formation in C. elegans embryos. Journal of Cell Biology 179: 397–402.

Wang JT and Seydoux G (2013) Germ cell specification. Advances in Experimental Medicine and Biology 757: 17–39.

Werts AD, Roh‐Johnson M and Goldstein B (2011) Dynamic localization of C. elegans TPR‐GoLoco proteins mediates mitotic spindle orientation by extrinsic signaling. Development 138: 4411–4422.

Zhang H, Skop AR and White JG (2008) Src and Wnt signaling regulate dynactin accumulation to the P2‐EMS cell border in C. elegans embryos. Journal of Cell Science 121: 155–161.

Zonies S, Motegi F, Hao Y and Seydoux G (2010) Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR‐2. Development 137: 1669–1677.

Further Reading

Begasse ML and Hyman AA (2011) The first cell cycle of the Caenorhabditis elegans embryo: spatial and temporal control of an asymmetric cell division. Results and Problems in Cell Differentiation 53: 109–133.

Goldstein B and Macara IG (2007) The PAR proteins: fundamental players in animal cell polarization. Developmental Cell 13: 609–622.

Riddle DL, Blumenthal T, Meyer BJ and Priess JR (1997) Introduction to C. elegans. In: Riddle DL, Blumenthal T, Meyer BJ and Priess JR (eds) C elegans II, chap. 1, p. 1–22. NY: Cold Spring Harbor.

St Johnston D and Ahringer J (2010) Cell polarity in eggs and epithelia: parallels and diversity. Cell 141: 757–774.

Werts AD and Goldstein B (2011) How signaling between cells can orient a mitotic spindle. Seminars in Cell and Developmental Biology 22: 842–849.

Web Link

WormBook: The online review of C elegans biology. http//

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Espiritu, Eugenel B, and Rose, Lesilee S(Apr 2013) Caenorhabditis elegans Embryo: Establishment of Asymmetry. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001506.pub3]