Asymmetries in Cell Division, Cell Size, and Furrowing in the Xenopus laevis Embryo

  • Jean-Pierre TassanEmail author
  • Martin Wühr
  • Guillaume Hatte
  • Jacek Kubiak
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 61)


Asymmetric cell divisions produce two daughter cells with distinct fate. During embryogenesis, this mechanism is fundamental to build tissues and organs because it generates cell diversity. In adults, it remains crucial to maintain stem cells. The enthusiasm for asymmetric cell division is not only motivated by the beauty of the mechanism and the fundamental questions it raises, but has also very pragmatic reasons. Indeed, misregulation of asymmetric cell divisions is believed to have dramatic consequences potentially leading to pathogenesis such as cancers. In diverse model organisms, asymmetric cell divisions result in two daughter cells, which differ not only by their fate but also in size. This is the case for the early Xenopus laevis embryo, in which the two first embryonic divisions are perpendicular to each other and generate two pairs of blastomeres, which usually differ in size: one pair of blastomeres is smaller than the other. Small blastomeres will produce embryonic dorsal structures, whereas the larger pair will evolve into ventral structures. Here, we present a speculative model on the origin of the asymmetry of this cell division in the Xenopus embryo. We also discuss the apparently coincident asymmetric distribution of cell fate determinants and cell-size asymmetry of the 4-cell stage embryo. Finally, we discuss the asymmetric furrowing during epithelial cell cytokinesis occurring later during Xenopus laevis embryo development.


Xenopus Embryo Asymmetric Cell Division Division Plane Cleavage Furrow Vegetal Pole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Michael V. Danilchik (Oregon Health and Sciences University, Portland, OR, USA) and Malgorzata Kloc (the Houston Methodist Hospital, Houston TX, USA) for helpful discussion and comments on the manuscript. We also thank the Microscopy Rennes Imaging Center (MRic, BIOSIT, IBiSA). Work in our lab was supported by le Centre National de la Recherche Scientifique (CNRS) and l’Agence Nationale de la Recherche (ANR, KinBioFRET). G.H. was supported by the MENESR and partly by a grant from the Ligue Nationale contre le Cancer. MW was supported by Princeton University start-up funding.


  1. Albertson R, Doe CQ (2003) Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nat Cell Biol 5:166–170CrossRefPubMedGoogle Scholar
  2. Audhya A, Hyndman F, McLeod IX et al (2005) A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans. J Cell Biol 171:267–279CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bauer DV, Huang S, Moody SA (1994) The cleavage stage origin of Spemann’s organizer: analysis of the movements of blastomere clones before and during gastrulation in Xenopus. Development 120:1179–1189PubMedGoogle Scholar
  4. Beckhelling C, Pérez-Mongiovi D, Houliston E (2000) Localised MPF regulation in eggs. Biol Cell 92:245–253CrossRefPubMedGoogle Scholar
  5. Black SD, Gerhart JC (1985) Experimental control of the site of embryonic axis formation in Xenopus laevis eggs centrifuged before first cleavage. Dev Biol 108:310–324CrossRefPubMedGoogle Scholar
  6. Bluemink JG, de Laat SW (1973) New membrane formation during cytokinesis in normal and cytochalasin B-treated eggs of Xenopus laevis. I. Electron microscope observations. J Cell Biol 59:89–108CrossRefPubMedPubMedCentralGoogle Scholar
  7. Byers TJ, Armstrong PB (1986) Membrane protein redistribution during Xenopus first cleavage. J Cell Biol 102:2176–2184CrossRefPubMedGoogle Scholar
  8. Carron C, Shi DL (2016) Specification of anteroposterior axis by combinatorial signaling during Xenopus development. Wiley Interdiscip Rev Dev Biol 5:150–168CrossRefPubMedGoogle Scholar
  9. Chalmers AD, Strauss B, Papalopulu N (2003) Oriented cell divisions asymmetrically segregate aPKC and generate cell fate diversity in the early Xenopus embryo. Development 130:2657–2668CrossRefPubMedGoogle Scholar
  10. Chang JB, Ferrell JE Jr (2013) Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle. Nature 500:603–607CrossRefPubMedPubMedCentralGoogle Scholar
  11. Danilchik MV, Black SD (1988) The first cleavage plane and the embryonic axis are determined by separate mechanisms in Xenopus laevis. I. Independence in undisturbed embryos. Dev Biol 128:58–64CrossRefPubMedGoogle Scholar
  12. Danilchik MV, Denegre JM (1991) Deep cytoplasmic rearrangements during early development in Xenopus laevis. Development 111:845–856PubMedGoogle Scholar
  13. Danilchik MV, Gerhart JC (1987) Differentiation of the animal-vegetal axis in Xenopus laevis oocytes. I. Polarized intracellular translocation of platelets establishes the yolk gradient. Dev Biol 122(1):101–112CrossRefPubMedGoogle Scholar
  14. Danilchik MV, Funk WC, Brown EE, Larkin K (1998) Requirement for microtubules in new membrane formation during cytokinesis of Xenopus embryos. Dev Biol 194:47–60. doi: 10.1006/dbio.1997.8815 CrossRefPubMedGoogle Scholar
  15. Danilchik MV, Bedrick SD, Brown EE, Ray K (2003) Furrow microtubules and localized exocytosis in cleaving Xenopus laevis embryos. J Cell Sci 116:273–283CrossRefPubMedGoogle Scholar
  16. Danilchik M, Williams M, Brown E (2013) Blastocoel-spanning filopodia in cleavage-stage Xenopus laevis: potential roles in morphogen distribution and detection. Dev Biol 382:70–81CrossRefPubMedGoogle Scholar
  17. De Domenico E, Owens ND, Grant IM, Gomes-Faria R, Gilchrist MJ (2015) Molecular asymmetry in the 8-cell stage Xenopus tropicalis embryo described by single blastomere transcript sequencing. Dev Biol 408:252–268CrossRefPubMedPubMedCentralGoogle Scholar
  18. de Laat WS, Bluemink JG (1974) New membrane formation during cytokinesis in normal and cytochalasin B-treated eggs of Xenopus laevis. II. Electrophysiological observations. J Cell Biol 60:529–540CrossRefPubMedPubMedCentralGoogle Scholar
  19. Elinson RP (1980) The amphibian egg cortex in fertilization and early development. In: The cell surface: mediator of developmental processes, pp 217–234Google Scholar
  20. Elinson RP, Rowning B (1988) A transient array of parallel microtubules in frog eggs: potential tracks for a cytoplasmic rotation that specifies the dorso-ventral axis. Dev Biol 128:185–197CrossRefPubMedGoogle Scholar
  21. Fesenko I, Kurth T, Sheth B, Fleming TP, Citi S, Hausen P (2000) Tight junction biogenesis in the early Xenopus embryo. Mech Dev 96:51–65CrossRefPubMedGoogle Scholar
  22. Founounou N, Loyer N, Le Borgne R (2013) Septins regulate the contractility of the actomyosin ring to enable adherens junction remodeling during cytokinesis of epithelial cells. Dev Cell 24:242–255CrossRefPubMedGoogle Scholar
  23. Gerhart J, Keller R (1986) Region-specific cell activities in amphibian gastrulation. Annu Rev Cell Biol 2:201–229CrossRefPubMedGoogle Scholar
  24. Gerhart J, Ubbels G, Black S, Hara K, Kirschner M (1981) A reinvestigation of the role of the gray crescent in axis formation in Xenopus laevis. Nature 292:511–517CrossRefPubMedGoogle Scholar
  25. Gerhart JC et al (1984) Localization and induction in early development of Xenopus. Philos Trans R Soc Lond B Biol Sci 307:319–330CrossRefPubMedGoogle Scholar
  26. Gerhart J, Danilchik M, Doniach T, Roberts S, Rowning B, Stewart R (1989) Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development. Development 107(Suppl):37–51PubMedGoogle Scholar
  27. Grant PA, Herold MB, Moody SA (2013) Blastomere explants to test for cell fate commitment during embryonic development. J Vis Exp. doi: 10.3791/4458 Google Scholar
  28. Glotzer M (1997) The mechanism and control of cytokinesis. Curr Opin Cell Biol 9:815823CrossRefGoogle Scholar
  29. Grill SW, Hyman AA (2005) Spindle positioning by cortical pulling forces. Dev Cell 8:461465CrossRefGoogle Scholar
  30. Guillot C, Lecuit T (2013) Adhesion disengagement uncouples intrinsic and extrinsic forces to drive cytokinesis in epithelial tissues. Dev Cell 24:227–241CrossRefPubMedGoogle Scholar
  31. Hatte G, Tramier M, Prigent C, Tassan JP (2014) Epithelial cell division in the Xenopus laevis embryo during gastrulation. Int J Dev Biol 58:775–781CrossRefPubMedGoogle Scholar
  32. Hausen P, Riebesell M (1991) The early development of Xenopus laevis: an altlas of the histology. Springer, New YorkGoogle Scholar
  33. Herszterg S, Leibfried A, Bosveld F, Martin C, Bellaiche Y (2013) Interplay between the dividing cell and its neighbors regulates adherens junction formation during cytokinesis in epithelial tissue. Dev Cell 24:256–270CrossRefPubMedGoogle Scholar
  34. Hertwig O (1893) Ueber den Werth der ersten Furchungszellen fuer die Organbildung des Embryo. Experimentelle Studien am Frosch- und Tritonei. Arch Mikr Anat xlii:662–807CrossRefGoogle Scholar
  35. Houliston E, Elinson RP (1991) Evidence for the involvement of microtubules, ER, and kinesin in the cortical rotation of fertilized frog eggs. J Cell Biol 114:1017–1028CrossRefPubMedGoogle Scholar
  36. Houston DW (2012) Cortical rotation and messenger RNA localization in Xenopus axis formation. Wiley Interdiscip Rev Dev Biol 1:371–388CrossRefPubMedGoogle Scholar
  37. Ibanez E, Albertini DF, Overstrom EW (2005) Effect of genetic background and activating stimulus on the timing of meiotic cell cycle progression in parthenogenetically activated mouse oocytes. Reproduction 129:27–38CrossRefPubMedGoogle Scholar
  38. Jinguji Y, Ishikawa H (1992) Electron microscopic observations on the maintenance of the tight junction during cell division in the epithelium of the mouse small intestine. Cell Struct Funct 17:27–37CrossRefPubMedGoogle Scholar
  39. Kageura H (1997) Activation of dorsal development by contact between the cortical dorsal determinant and the equatorial core cytoplasm in eggs of Xenopus laevis. Development 124:1543–1551PubMedGoogle Scholar
  40. Kalt MR (1971a) The relationship between cleavage and blastocoel formation in Xenopus laevis. I. Light microscopic observations. J Embryol Exp Morphol 26:37–49PubMedGoogle Scholar
  41. Kalt MR (1971b) The relationship between cleavage and blastocoel formation in Xenopus laevis. II. Electron microscopic observations. J Embryol Exp Morphol 26:51–66PubMedGoogle Scholar
  42. Keller R (2002) Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298:1950–1954CrossRefPubMedGoogle Scholar
  43. Kikkawa M, Takano K, Shinagawa A (1996) Location and behavior of dorsal determinants during first cell cycle in Xenopus eggs. Development 122:3687–3696PubMedGoogle Scholar
  44. King ML, Zhou Y, Bubunenko M (1999) Polarizing genetic information in the egg: RNA localization in the frog oocyte. Bioessays 21:546–557CrossRefPubMedGoogle Scholar
  45. Klein SL (1987) The first cleavage furrow demarcates the dorsal-ventral axis in Xenopus embryos. Dev Biol 120:299–304CrossRefPubMedGoogle Scholar
  46. Kloc M, Etkin LD (1994) Delocalization of Vg1 mRNA from the vegetal cortex in Xenopus oocytes after destruction of Xlsirt RNA. Science 265:1101–1103CrossRefPubMedGoogle Scholar
  47. Larabell CA, Torres M, Rowning BA, Yost C, Miller JR, Wu M, Kimelman D, Moon RT (1997) Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway. J Cell Biol 136:1123–1136CrossRefPubMedPubMedCentralGoogle Scholar
  48. Le Page Y, Chartrain I, Badouel C, Tassan JP (2011) A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development. J Cell Sci 124:958–968CrossRefPubMedGoogle Scholar
  49. Lecuit T, Wieschaus E (2000) Polarized insertion of new membrane from a cytoplasmic reservoir during cleavage of the Drosophila embryo. J Cell Biol 150:849–860CrossRefPubMedPubMedCentralGoogle Scholar
  50. Maddox AS, Lewellyn L, Desai A, Oegema K (2007) Anillin and the septins promote asymmetric ingression of the cytokinetic furrow. Dev Cell 12:827–835CrossRefPubMedGoogle Scholar
  51. Marrari Y, Rouvière C, Houliston E (2004) Complementary roles for dynein and kinesins in the Xenopus egg cortical rotation. Dev Biol 271:38–48CrossRefPubMedGoogle Scholar
  52. Martin-Belmonte F, Perez-Moreno M (2011) Epithelial cell polarity, stem cells and cancer. Nat Rev Cancer 12:23–38PubMedGoogle Scholar
  53. Masho R (1990) Close correlation between the first cleavage plane and the body axis in early Xenopus embryos. Dev Growth Differ 32:57–64CrossRefGoogle Scholar
  54. Merzdorf CS, Chen YH, Goodenough DA (1998) Formation of functional tight junctions in Xenopus embryos. Dev Biol 195:187–203CrossRefPubMedGoogle Scholar
  55. Mitchison TJ, Ishihara K, Nguyen P, Wühr M (2015) Size scaling of microtubule assemblies in early Xenopus embryos. Cold Spring Harb Perspect Biol 7:a019182CrossRefPubMedGoogle Scholar
  56. Moody SA, Kline MJ (1990) Segregation of fate during cleavage of frog (Xenopus laevis) blastomeres. Anat Embryol (Berl) 182:347–362CrossRefGoogle Scholar
  57. Morais-de-Sá E, Sunkel C (2013) Adherens junctions determine the apical position of the midbody during follicular epithelial cell division. EMBO Rep 14:696–703CrossRefPubMedPubMedCentralGoogle Scholar
  58. Mowry KL, Cote CA (1999) RNA sorting in Xenopus oocytes and embryos. Faseb J 13:435–445PubMedGoogle Scholar
  59. Nieuwkoop PD, Faber J (1967) Normal table of Xenopus laevis (Daudin). North-Holland, AmsterdamGoogle Scholar
  60. Pérez-Mongiovi D, Chang P, Houliston E (1998) A propagated wave of MPF activation accompanies surface contraction waves at first mitosis in Xenopus. J Cell Sci 111(Pt 3):385–393PubMedGoogle Scholar
  61. Prodon F, Chenevert J, Hebras C et al (2010) Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors. Development 137:2011–2021CrossRefPubMedGoogle Scholar
  62. Rankin S, Kirschner MW (1997) The surface contraction waves of Xenopus eggs reflect the metachronous cell-cycle state of the cytoplasm. Curr Biol 7:451–454CrossRefPubMedGoogle Scholar
  63. Reinsch S, Karsenti E (1994) Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J Cell Biol 126:1509–1526CrossRefPubMedGoogle Scholar
  64. Sakai M (1996) The vegetal determinants required for the Spemann organizer move equatorially during the first cell cycle. Development 122:2207–2214PubMedGoogle Scholar
  65. Scharf SR, Gerhart JC (1980) Determination of the dorsal-ventral axis in eggs of Xenopus laevis: complete rescue of uv-impaired eggs by oblique orientation before first cleavage. Dev Biol 79:181–198CrossRefPubMedGoogle Scholar
  66. Schneider S, Steinbeisser H, Warga RM, Hausen P (1996) Beta-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos. Mech Dev 57:191–198CrossRefPubMedGoogle Scholar
  67. Schroeder MM, Gard DL (1992) Organization and regulation of cortical microtubules during the first cell cycle of Xenopus eggs. Development 114:699–709PubMedGoogle Scholar
  68. Souza KA, Black SD, Wassersug RJ (1995) Amphibian development in the virtual absence of gravity. Proc Natl Acad Sci U S A 92:1975–1978CrossRefPubMedPubMedCentralGoogle Scholar
  69. Stewart-savage J, Grey RD (1982) The temporal and spatial relationships between cortical contraction, sperm trail formation and pronuclear migration in fertilized Xenopus eggs. Wilhelm Rouxs Arch Dev Biol 191:241–245CrossRefGoogle Scholar
  70. Ubbels GA, Hara K, Koster CH, Kirschner MW (1983) Evidence for a functional role of the cytoskeleton in determination of the dorsoventral axis in Xenopus laevis eggs. J Embryol Exp Morphol 77:15–37PubMedGoogle Scholar
  71. Vincent JP, Gerhart JC (1987) Subcortical rotation in Xenopus eggs: an early step in embryonic axis specification. Dev Biol 123:526–539CrossRefPubMedGoogle Scholar
  72. Vincent JP, Oster GF, Gerhart JC (1986) Kinematics of gray crescent formation in Xenopus eggs: the displacement of subcortical cytoplasm relative to the egg surface. Dev Biol 113:484–500CrossRefPubMedGoogle Scholar
  73. Wang Q, Racowsky C, Deng M (2011) Mechanism of the chromosome-induced polar body extrusion in mouse eggs. Cell Div 6:17CrossRefPubMedPubMedCentralGoogle Scholar
  74. Wühr M, Dumont S, Groen AC, Needleman DJ, Mitchison TJ (2009) How does a millimeter-sized cell find its center? Cell Cycle 8:1115–1121CrossRefPubMedPubMedCentralGoogle Scholar
  75. Wühr M, Tan ES, Parker SK, Detrich HW 3rd, Mitchison TJ (2010) A model for cleavage plane determination in early amphibian and fish embryos. Curr Biol 20:2040–2045CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Jean-Pierre Tassan
    • 1
    • 2
    Email author
  • Martin Wühr
    • 3
  • Guillaume Hatte
    • 1
    • 2
  • Jacek Kubiak
    • 1
    • 2
  1. 1.RennesFrance
  2. 2.Université de Rennes 1, Institut de Génétique et Développement de RennesRennesFrance
  3. 3.Department of Molecular Biology and the Lewis-Sigler Institute for Integrative GenomicsPrinceton UniversityPrincetonUSA

Personalised recommendations