Key Points
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Asymmetric cell division can be divided into four main steps: symmetry breaking, polarity establishment, determinant segregation and spindle positioning. As a result of these steps, a mother cell can give rise to two daughter cells with different fates.
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Symmetry breaking and polarity establishment are exemplified using the one-cell Caenorhabditis elegans embryo. This example illustrates the general principle whereby local modulation of the actin cytoskeleton is crucial for symmetry breaking and for polarity establishment.
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The mechanisms by which cell polarity is translated into segregation of fate determinants are reviewed, with an emphasis on Drosophila melanogaster neuroblasts. In addition, the importance of regulated trafficking in ensuring proper cell-fate acquisition is illustrated using the example of D. melanogaster sensory organ precursors.
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The mechanisms by which cell polarity is coupled to spindle positioning are covered, focusing again on the one-cell C. elegans embryo. Here, the available evidence indicates that spindle positioning is mediated by microtubule depolymerization and dynein function, as well as by heterotrimeric G proteins and associated components.
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The consequences for proliferation control of defective asymmetric division of D. melanogaster neuroblasts are reviewed, and these underscore why findings in flies and worms are relevant for understanding self-renewing normal and cancer stem cells.
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The review also includes a brief discussion of asymmetric cell division in vertebrates, and provides a taster of some promising directions for this exciting field.
Abstract
Asymmetric cell division is fundamental for generating diversity in multicellular organisms. The mechanisms that govern asymmetric cell division are increasingly well understood, owing notably to studies that were conducted in Drosophila melanogaster and Caenorhabditis elegans. Lessons learned from these two model organisms also apply to cells that divide asymmetrically in other metazoans, such as self-renewing stem cells in mammals.
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Acknowledgements
I am grateful to K. Afshar, D. Constam, V. Hachet and J. Knoblich for critical reading of the manuscript, and to J. Knoblich also for providing the movie for Supplementary information S1. Apologies go to those authors whose work could not be covered owing to space constraints. My laboratory is supported by grants from the Swiss National Science Foundation (3100A0-102087) and Oncosuisse (OCS-01676-02-2005, OCS KLS 02024-02-2007).
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Supplementary information
Supplementary information S1 (movie) | Asymmetric division of a Drosophila SOP
D. melanogaster sensory organ precursor (SOP) cell expressing GFP-Pon (green) and Histone2B-RFP (red). Anterior is to the left. The SOP is ∼ 10 µm in diameter. Note that GFPPon is segregated to the anterior of the SOP, and is thus inherited by pIIb. Modified with permission from ref. 1. (MOV 3318 kb)
Supplementary information S2 (movie) | Asymmetric division of a one-cell stage C. elegans embryo
C. elegans embryo expressing GFP-PIE-1 (green) and imaged using dual time-lapse DIC and fluorescence microscopy; the GFP and DIC images have been overlaid. Anterior is to the left. The embryo is ∼50 µm-long. Note that the bulk of GFP-PIE-1 is segregated to the posterior of the one-cell embryo. (MOV 8310 kb)
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Glossary
- Mitotic spindle
-
A highly dynamic array of microtubules that forms during mitosis and serves to move the sister chromatids apart.
- Cell cortex
-
The region underlying the plasma membrane that is rich in actin filaments and associated proteins.
- Pronucleus
-
The haploid nucleus that is derived from either sperm or oocyte and that is present in the newly fertilized zygote.
- Centrosome
-
The principal microtubule-organizing centre of animal cells, an organelle that contains the centrioles and that anchors the minus end of microtubules.
- PAR proteins
-
A set of six proteins that were initially identified in C. elegans and whose inactivation results in a partitioning-defective phenotype in early embryos.
- PDZ domain
-
A protein-interaction domain that is often found in scaffolding proteins and that is named after the founding members of this protein family (PSD-95, discs-large and ZO-1).
- Ring finger
-
A protein domain that consists of two loops that are held together at their base by Cys and His residues that form a complex with two zinc ions. Many ring fingers function in protein degradation by facilitating protein ubiquitylation.
- 14–3–3 proteins
-
Adaptor/scaffold proteins that form homo- and heterodimers and bind, through specialized phosphorylated peptide motifs, to various proteins that are involved notably in signal transduction and in cell-cycle control.
- Neurectoderm
-
A portion of the ectoderm that is destined to become neural tissue.
- Coiled-coil domain
-
A structural domain that can mediate oligomerization. Coiled-coils contain two to five helices that twist around each other to form a supercoil.
- t-SNARE
-
An integral membrane protein that is present on a target membrane or organelle and that mediates fusion through interaction with a v-SNARE partner protein that is located on the fusion partner.
- Sheath cell
-
One of the four cells that comprises the bristle sensory organ that derives from the SOP in the peripheral nervous system of D. melanogaster.
- Socket cell
-
One of the four cells that comprises the bristle sensory organ that derives from the sensory organ precursors in the peripheral nervous system of D. melanogaster.
- Aggresome
-
Cytoplasmic inclusions bodies that contain misfolded proteins and that are located near centrosomes.
- Proteasome
-
A large protein complex that is responsible for degrading intracellular proteins that have been targeted for destruction, usually by the addition of ubiquitin polymers.
- Niche cell
-
A cell that is located in the vicinity of stem cells and that provides a suitable environment for maintaining the self-renewing capacity of stem cells.
- Gonial cell
-
A germ cell before it enters the meiotic cell cycle.
- Recycling endosome
-
An intracellular membrane compartment that mediates the recycling of endocytosed material back to the plasma membrane.
- Blastomere
-
A cell that is generated during embryonic cleavage divisions.
- Astral microtubules
-
Microtubules that radiate from the mitotic spindle poles to the cell cortex. They are involved in positioning the spindle poles during cell division.
- Kinetochore
-
A multiprotein complex that assembles on centromeric DNA and that mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.
- Ventricular zone
-
A layer of cells that is located immediately adjacent to the cerebral ventricles in the vertebrate brain.
- Adherens junction
-
A cell–cell adhesion complex that contains cadherins and catenins that are attached to cytoplasmic actin filaments.
- Basement membrane
-
A thin layer of connective tissue that underlies the epithelium of many organs.
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Gönczy, P. Mechanisms of asymmetric cell division: flies and worms pave the way. Nat Rev Mol Cell Biol 9, 355–366 (2008). https://doi.org/10.1038/nrm2388
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DOI: https://doi.org/10.1038/nrm2388
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