Daughter Cells Of Different Sizes Research Articles

The people behind the papers - Thomas Mullan and Richard Poole.

Asymmetric cell divisions can produce daughter cells of different sizes, but it is unclear whether unequal cell cleavage is important for cell fate decisions. A new paper in Development explores the role of unequal cleavages in Caenorhabditis elegans embryos. To learn more about the story behind the paper, we caught up with first author Thomas Mullan and corresponding author Richard Poole, Associate Professor of Developmental Biology at University College London, UK.

On existence and uniqueness of solutions to a pantograph type equation

We show existence and uniqueness of solutions to an initial boundary value problem that entails a pantograph type functional partial differential equation with two advanced nonlocal terms. The problem models cell growth and division into two daughter cells of different sizes. There is a paucity of information about the solution to the problem for an arbitrary initial cell distribution. doi:10.1017/S144618112100002X

Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis.

Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division of Caenorhabditis elegans embryos, which yields a large AB cell and a small P1 cell. We equalized AB and P1 sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1 descendants, as well as defects in cell positioning, division orientation, and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development of C. elegans.

ON EXISTENCE AND UNIQUENESS OF SOLUTIONS TO A PANTOGRAPH TYPE EQUATION

AbstractWe show existence and uniqueness of solutions to an initial boundary value problem that entails a pantograph type functional partial differential equation with two advanced nonlocal terms. The problem models cell growth and division into two daughter cells of different sizes. There is a paucity of information about the solution to the problem for an arbitrary initial cell distribution.

Caenorhabditis elegans CES-1 Snail Represses pig-1 MELK Expression To Control Asymmetric Cell Division.

Snail-like transcription factors affect stem cell function through mechanisms that are incompletely understood. In the Caenorhabditis elegans neurosecretory motor neuron (NSM) neuroblast lineage, CES-1 Snail coordinates cell cycle progression and cell polarity to ensure the asymmetric division of the NSM neuroblast and the generation of two daughter cells of different sizes and fates. We have previously shown that CES-1 Snail controls cell cycle progression by repressing the expression of cdc-25.2 CDC25. However, the mechanism through which CES-1 Snail affects cell polarity has been elusive. Here, we systematically searched for direct targets of CES-1 Snail by genome-wide profiling of CES-1 Snail binding sites and identified >3000 potential CES-1 Snail target genes, including pig-1, the ortholog of the oncogene maternal embryonic leucine zipper kinase (MELK). Furthermore, we show that CES-1 Snail represses pig-1 MELK transcription in the NSM neuroblast lineage and that pig-1 MELK acts downstream of ces-1 Snail to cause the NSM neuroblast to divide asymmetrically by size and along the correct cell division axis. Based on our results we propose that by regulating the expression of the MELK gene, Snail-like transcription factors affect the ability of stem cells to divide asymmetrically and, hence, to self-renew. Furthermore, we speculate that the deregulation of MELK contributes to tumorigenesis by causing cells that normally divide asymmetrically to divide symmetrically instead.

A model for asymmetrical cell division.

We present a model that describes the growth, division and death of a cell population structured by size. The model is an extension of that studied by Hall and Wake (1989) and incorporates the asymmetric division of cells. We consider the case of binary asymmetrical splitting in which a cell of size ε divides into two daughter cells of different sizes and find the steady size distribution (SSD) solution to the non-local differential equation. We then discuss the shape of the SSD solution. The existence of higher eigenfunctions is also discussed.

The DEP domain-containing protein TOE-2 promotes apoptosis in the Q lineage of C. elegans through two distinct mechanisms

Neuroblast divisions in the nematode Caenorhabditis elegans often give rise to a larger neuron and a smaller cell that dies. We have previously identified genes that, when mutated, result in neuroblast divisions that generate daughter cells that are more equivalent in size. This effect correlates with the survival of daughter cells that would normally die. We now describe a role for the DEP domain-containing protein TOE-2 in promoting the apoptotic fate in the Q lineage. TOE-2 localized at the plasma membrane and accumulated in the cleavage furrow of the Q.a and Q.p neuroblasts, suggesting that TOE-2 might position the cleavage furrow asymmetrically to generate daughter cells of different sizes. This appears to be the case for Q.a divisions where loss of TOE-2 led to a more symmetric division and to survival of the smaller Q.a daughter. Localization of TOE-2 to the membrane is required for this asymmetry, but, surprisingly, the DEP domain is dispensable. By contrast, loss of TOE-2 led to loss of the apoptotic fate in the smaller Q.p daughter but did not affect the size asymmetry of the Q.p daughters. This function of TOE-2 required the DEP domain but not localization to the membrane. We propose that TOE-2 ensures an apoptotic fate for the small Q.a daughter by promoting asymmetry in the daughter cell sizes of the Q.a neuroblast division but by a mechanism that is independent of cell size in the Q.p division.

Asymmetric cortical extension leads to asymmetric cell division in Drosophila neuroblasts

Drosophila neuroblasts divide asymmetrically to produce two daughter cells of different sizes: a larger neuroblast and a smaller ganglion mother cell (GMC). Live imaging of neuroblasts demonstrates that they divide asymmetrically due to the localization of myosin to the basal pole of the neuroblast (the side that will become the smaller GMC) during anaphase. We hypothesized that this asymmetric myosin localization would lead to reduced extension at the basal pole while extension at the apical pole would not be restricted. We measured the position of the apical and the basal cortex in neuroblasts and observed preferential displacement of the apical cortex that becomes the larger daughter cell during anaphase, effectively shifting the cleavage furrow toward the smaller daughter cell. In neuroblasts the apical pole extends ~3 times more than the basal pole producing an apical daughter cell (neuroblast) that is ~2 times larger than the basal daughter cell (GMC). In mutants that have lost the basal myosin domain, Pins (Partner of Inscuteable) and Gβ, there is equal cortical extension at both poles and the division produces daughter cells of equal size. This asymmetry is not due to unequal addition of membrane at the apical pole as the amount of surface area created during mitosis (determined by 3D reconstruction of the cell) is insignificant compared to the difference in surface area between the daughter cells. We propose a model in which contraction‐driven asymmetric polar extension of the neuroblast cortex during anaphase contributes to asymmetric furrow position and daughter cell size. National Institutes of Health Grant 068032.

Asymmetric Cell Division: A New Way to Divide Unequally

It has long been known that cells can divide unequally by shifting the mitotic spindle to one side. Two recent reports identify an alternative way to generate daughter cells of different sizes.

Positioning cytokinesis

Cytokinesis is the terminal step of the cell cycle during which a mother cell divides into daughter cells. Often, the machinery of cytokinesis is positioned in such a way that daughter cells are born roughly equal in size. However, in many specialized cell types or under certain environmental conditions, the cell division machinery is placed at nonmedial positions to produce daughter cells of different sizes and in many cases of different fates. Here we review the different mechanisms that position the division machinery in prokaryotic and eukaryotic cell types. We also describe cytokinesis-positioning mechanisms that are not adequately explained by studies in model organisms and model cell types.

Morphology and phylogenetic position of Spongiochrysis hawaiiensis gen. et sp. nov., the first known terrestrial member of the order Cladophorales (Ulvophyceae, Chlorophyta)

Spongiochrysis hawaiiensis gen. et sp. nov. is described from material collected at two sites on O'ahu, Hawaiian Islands. This alga produced golden-yellow crusts on the bark of Casuarina trees and consisted of globular cells with an axial stellate chloroplast. The only form of reproduction was a specialized type of autosporulation in which a budding-like division of the mother cell produced daughter cells of different sizes. Phylogenetic analyses of the 18S rRNA gene showed that Spongiochrysis hawaiiensis is a member of the freshwater clade of the Cladophorales/Siphonocladales lineage in the green algal class Ulvophyceae. On the basis of its unicellular habit and terrestrial habitat, this species is well differentiated from all other members of the same lineage and can be considered as the first known successful step of a member of the order Cladophorales into terrestrial habitats. The implications of the description of this species with regard to both green algal evolution and conservation of little-known tropical habitats are discussed. The holotype specimen of Spongiochrysis hawaiiensis is GALW015489 and isotype specimens have also been deposited in the BISH and BM herbaria.

A new aerial alga, Stichococcus ampulliformis sp. nov. (Trebouxiophyceae, Chlorophyta) from Japan

SUMMARY A new aerial alga, Stichococcus ampulliformis S. Handa sp. nov. (Trebouxiophyceae, Chlorophyta) is described based on a clone isolated from the bark of Cephalotaxus harringtonia (Knight ex Forbes) K. Koch collected from Taishaku-kyo Gorge, Hiroshima Prefecture, south-west Japan. This alga was examined by light microscopy and transmission electron microscopy and subjected to molecular phylogenetic analysis. Based on its morphological features and life-cycle, especially short filament formation, the alga was assigned to the genus Stichococcus Nageli. However, this alga differs from other described Stichococcus species in that it reproduces by a form of ‘budding’, producing two daughter cells of different sizes. The larger cell, enclosed within the mother cell wall, soon reaches the size of a normal vegetative cell. The smaller cell is extruded and takes longer to reach full vegetative size. A phylogenetic tree constructed using 18S rRNA sequences indicated that, within the Trebouxiophyceae, S. ampulliformis is closely related to S. bacillaris Nageli and some species of Prasiola Meneghini.

Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo.

Cell divisions that create daughter cells of different sizes are crucial for the generation of cell diversity during animal development. In such asymmetric divisions, the mitotic spindle must be asymmetrically positioned at the end of anaphase. The mechanisms by which cell polarity translates to asymmetric spindle positioning remain unclear. Here we examine the nature of the forces governing asymmetric spindle positioning in the single-cell-stage Caenorhabditis elegans embryo. To reveal the forces that act on each spindle pole, we removed the central spindle in living embryos either physically with an ultraviolet laser microbeam, or genetically by RNA-mediated interference of a kinesin. We show that pulling forces external to the spindle act on the two spindle poles. A stronger net force acts on the posterior pole, thereby explaining the overall posterior displacement seen in wild-type embryos. We also show that the net force acting on each spindle pole is under control of the par genes that are required for cell polarity along the anterior-posterior embryonic axis. Finally, we discuss simple mathematical models that describe the main features of spindle pole behaviour. Our work suggests a mechanism for generating asymmetry in spindle positioning by varying the net pulling force that acts on each spindle pole, thus allowing for the generation of daughter cells with different sizes.

Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system.

The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and position of the mitotic spindle. In the Drosophila embryo, the determinant Prospero is localized basally and is segregated equally to daughters of similar cell size during epidermal cell division. In contrast, during neuroblast division Prospero is segregated asymmetrically to the smaller daughter cell. This simple switch between symmetric and asymmetric segregation is achieved by changing the orientation of cell division: neural cells divide in a plane perpendicular to that of epidermoblast division. Here, by labelling mitotic spindles in living Drosophila embryos, we show that neuroblast spindles are initially formed in the same axis as epidermal cells, but rotate before cell division. We find that daughter cells of different sizes arise because the spindle itself becomes asymmetric at anaphase: apical microtubules elongate, basal microtubules shorten, and the midbody moves basally until it is positioned asymmetrically between the two spindle poles. This observation contradicts the widely held hypothesis that the cleavage furrow is always placed midway between the two centrosomes.

Unequal Cell Division as a Driving Force During Differentiation

Unequal cell division, leading to daughter cells of different sizes, is a common event during development. We have formulated a model that shows how different cell sizes can lead to significant differences in the expression of an activator gene. The model is based on well-known aspects of the regulation of gene expression, specifically the existence of multiple regulatory sites, positive autoregulation, and the short half-life of regulatory proteins. Thus the daughter cells may follow distinct differentiation pathways even if there were no localized determinants in the mother cell.