Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early Caenorhabditis elegans development

Proper positioning of cells is essential for many aspects of development. Daughter cell positions can be specified via orienting the cell division axis during cytokinesis. Rotatory actomyosin flows during division have been implied in specifying and reorienting the cell division axis, but how general such reorientation events are, and how they are controlled, remains unclear. We followed the first nine divisions of Caenorhabditis elegans embryo development and demonstrate that chiral counter-rotating flows arise systematically in early AB lineage, but not in early P/EMS lineage cell divisions. Combining our experiments with thin film active chiral fluid theory we identify a mechanism by which chiral counter-rotating actomyosin flows arise in the AB lineage only, and show that they drive lineage-specific spindle skew and cell reorientation events. In conclusion, our work sheds light on the physical processes that underlie chiral morphogenesis in early development.

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Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early development

10.1101/842922 ◽

2019 ◽

Cited By ~ 2

Author(s):

Lokesh Pimpale ◽

Teije C. Middelkoop ◽

Alexander Mietke ◽

Stephan W. Grill

Keyword(s):

Cell Division ◽

Cell Lineage ◽

Early Embryo ◽

Embryonic Cell ◽

Rotating Flows ◽

Cell Divisions ◽

Fluid Theory ◽

Division Axis ◽

Cell Reorientation ◽

Shed Light

ABSTRACTProper positioning of cells is important for many aspects of embryonic development, tissue homeostasis, and regeneration. A simple mechanism by which cell positions can be specified is via orienting the cell division axis. This axis is specified at the onset of cytokinesis, but can be reoriented as cytokinesis proceeds. Rotatory actomyosin flows have been implied in specifying and reorienting the cell division axis in certain cases, but how general such reorientation events are, and how they are controlled, remains unclear. In this study, we set out to address these questions by investigating early Caenorhabditis elegans development. In particular, we determined which of the early embryonic cell divisions exhibit chiral counter-rotating actomyosin flows, and which do not. We follow the first nine divisions of the early embryo, and discover that chiral counter-rotating flows arise systematically in the early AB lineage, but not in early P/EMS lineage cell divisions. Combining our experiments with thin film active chiral fluid theory we identify specific properties of the actomyosin cortex in the symmetric AB lineage divisions that favor chiral counter-rotating actomyosin flows of the two halves of the dividing cell. Finally, we show that these counter-rotations are the driving force of both the AB lineage spindle skew and cell reorientation events. In conclusion, we here have shed light on the physical basis of lineage-specific actomyosin-based processes that drive chiral morphogenesis during development.

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ISOLATION AND GENETIC CHARACTERIZATION OF CELL-LINEAGE MUTANTS OF THE NEMATODE CAENORHABDITIS ELEGANS

Genetics ◽

10.1093/genetics/96.2.435 ◽

1980 ◽

Vol 96 (2) ◽

pp. 435-454 ◽

Cited By ~ 20

Author(s):

H Robert Horvitz ◽

John E Sulston

Keyword(s):

Caenorhabditis Elegans ◽

Cell Lineage ◽

Embryonic Cell ◽

Null Alleles ◽

Recessive Mutation ◽

Incomplete Penetrance ◽

Nematode Caenorhabditis Elegans ◽

Cell Lineages ◽

Cell Divisions ◽

Recessive Mutations

ABSTRACT Twenty-four mutants that alter the normally invariant post-embryonic cell lineages of the nematode Caenorhabditis elegans have been isolated and genetically characterized. In some of these mutants, cell divisions fail that occur in wild-type animals; in other mutants, cells divide that do not normally do so. The mutants differ in the specificities of their defects, so that it is possible to identify mutations that affect some cell lineages but not others. These mutants define 14 complementation groups, which have been mapped. The abnormal phenotype of most of the cell-lineage mutants results from a single recessive mutation; however, the excessive cell divisions characteristic of one strain, CB1322, require the presence of two unlinked recessive mutations. All 24 cell-lineage mutants display incomplete penetrance and/or variable expressivity. Three of the mutants are suppressed by pleiotropic suppressors believed to be specific for null alleles, suggesting that their phenotypes result from the complete absence of gene activity.

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The ncl-1 gene and genetic mosaics of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/141.3.989 ◽

1995 ◽

Vol 141 (3) ◽

pp. 989-1006 ◽

Cited By ~ 4

Author(s):

E M Hedgecock ◽

R K Herman

Keyword(s):

Cell Division ◽

Caenorhabditis Elegans ◽

Embryonic Cell ◽

Vulval Development ◽

Genetic Mosaics ◽

Cell Divisions ◽

Mosaic Analysis ◽

A Cell ◽

Intercellular Signal

Abstract A ncl-1 mutation results in enlarged nucleoli, which can be detected in nearly all cells of living animals by Nomarski microscopy. Spontaneous mitotic loss of a ncl-1(+)-containing free duplication in an otherwise homozygous ncl-1 mutant animal results in mosaicism for ncl-1 expression, and the patterns of mosaicism lead us to conclude that ncl-1 acts cell autonomously. The probability of mitotic loss of the duplication sDp3 is approximately constant over many cell divisions. About 60% of the losses of sDp3 at the first embryonic cell division involve nondisjunction. Frequencies of mitotic loss of different ncl-1(+)-bearing free duplications varied over a 200-fold range. The frequencies of mitotic loss were enhanced by a chromosomal him-10 mutation. We have used ncl-1 as a cell autonomous marker in the mosaic analysis of dpy-1 and lin-37. The focus of action of dpy-1 is in hypodermis. A mutation in lin-37 combined with a mutation in another gene results in a synthetic multivulva phenotype. We show that lin-37 acts cell nonautonomously and propose that it plays a role, along with the previously studied gene lin-15, in the generation of an intercellular signal by hyp7 that represses vulval development.

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Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator inC. elegans

Development ◽

10.1242/dev.129.9.2155 ◽

2002 ◽

Vol 129 (9) ◽

pp. 2155-2165

Author(s):

Ivana Kostić ◽

Richard Roy

Keyword(s):

Cell Cycle ◽

Cell Division ◽

Ectopic Expression ◽

Cell Lineage ◽

Intestinal Cells ◽

Specific Cell ◽

Cell Cycle Regulators ◽

Loss Of Function ◽

C Elegans ◽

Cell Divisions

The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.

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Mafb Restricts M-CSF Instructed Lineage Choice in HSC

Blood ◽

10.1182/blood.v116.21.sci-15.sci-15 ◽

2010 ◽

Vol 116 (21) ◽

pp. SCI-15-SCI-15

Author(s):

Michael H. Sieweke

Keyword(s):

Transcription Factor ◽

Stem Cell ◽

Cell Division ◽

Daughter Cell ◽

Critical Role ◽

Lineage Commitment ◽

Cytokine Signaling ◽

Self Renewal ◽

Cell Divisions ◽

Asymmetric Divisions

Abstract Abstract SCI-15 HSC need to enter the cycle to continuously regenerate mature blood cells in a correctly balanced ratio or to replenish the stem cell pool under stress conditions. Cell division of HSC may thus result in self-renewal divisions or the production of more differentiated progeny. Although such downstream progenitors still retain a high degree of multi-potency, recent advances in their characterization also suggest that early diversification into cells with distinct lineage bias can occur at the most primitive stem and precursor cell level. Whereas multiple cellular regulators have been identified that affect self-renewal of HSC, regulators that selectively control lineage specific commitment divisions of HSC are only beginning to be elucidated. Both transcription factor and cytokine signaling may play important roles in lineage engagement but it has been a long-standing debate, whether cytokine signaling has instructive or permissive effects on lineage commitment. In this context we reported that deficiency for the monocytic transcription factor MafB specifically sensitized HSC populations to M-CSF induced cell division and myeloid lineage commitment. We observed that MafB deficiency resulted in a specific up-regulation of the early myeloid transcription factor PU.1 and a dramatically enhanced myeloid specific repopulation activity that did not affect self-renewal or differentiation into other lineages. Our results point to a role for MafB in the maintenance of a balanced lineage potential of HSC by selectively restricting myeloid commitment divisions that give rise to PU.1+ progenitors in response to M-CSF signaling. Together this suggests that the potential of stem cells to produce differentiated progeny of a specific lineage bias can be subject to control by integrated cytokine/transcription factor circuits, where variation in cell intrinsic sensitivity limits like those set by MafB can render external cues such as M-CSF instructive. Stem cell self renewal or differentiation is associated with two different types of cell divisions, namely symmetric divisions that generate two identical daughter cells, or asymmetric divisions that produce a daughter cell with maintained stem cell properties and a daughter cell committed to a specific differentiation pathway. Our observation that reduced MafB levels specifically increased M-CSF stimulated asymmetric divisions giving rise to PU.1−/PU.1+ daughter pairs provides a conclusive explanation why increased myeloid commitment of MafB−/− HSC does not come at the expense of self-renewal or other lineages. The micro-environment can play a critical role in specifying the symmetry of cell divisions, but so far, investigations have focused on niche micro-environments that support HSC self-renewal. It is unknown whether environments also exist that support HSC commitment to specific lineages by enabling asymmetric divisions at the niche border. Using video-imaging approaches and genetic manipulation of the stem cell and stromal cell compartments we explore how cues from the microenvironment can affect asymmetric HSC division and lineage commitment. Disclosures: No relevant conflicts of interest to declare.

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Comparing Cell Division- and Cell Reproduction-based Cell Lineage Analysis for Early Embryogenesis of Caenorhabditis elegans

10.1101/199604 ◽

2017 ◽

Author(s):

Shi V. Liu

Keyword(s):

Cell Division ◽

Caenorhabditis Elegans ◽

Mother Cell ◽

Cell Lineage ◽

Early Embryogenesis ◽

Reconstruction Method ◽

Daughter Cells ◽

Cell Reproduction ◽

A Cell ◽

Lineage Analysis

ABSTRACTCell lineage analysis holds important stakes for understanding heredity and cell differentiation. Conventional cell lineages are reconstructed according to a cell division doctrine of one mother cell dividing into two daughter cells. An alternative cell lineage reconstruction method followed a cell reproduction discovery of multiple daughter cells reproduced from a same mother cell. To see which reconstruction method reflects reality of early embryogenesis of Caenorhabditis elegans, a side-by-side comparison was made between two methods. Here I show cell division-based lineage distorted reality and failed in revealing any true genealogy. Cell reproduction – based lineage conformed to reality with exact same number of cells in every developmental stage under examination and showed clear genealogical relationship. A paradigm-shift from cell division-to cell reproduction-based cell lineage analysis is necessary for correct understanding of developmental biology and will lead to a revolution in cell biology and life science.

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The Ultrastructure of the Nuclear Events of Binary Fission in Paramecium bursaria and the Effects of Colchicine on Cell Division

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051396 ◽

1974 ◽

Vol 32 ◽

pp. 276-277

Author(s):

L. M. Lewis

Keyword(s):

Cell Division ◽

Nuclear Envelope ◽

Condensed Chromatin ◽

Binary Fission ◽

Paramecium Bursaria ◽

Nuclear Events ◽

Division Axis

The effects of colchicine on extranuclear microtubules associated with the macronucleus of Paramecium bursaria were studied to determine the possible role that these microtubules play in controlling the shape of the macronucleus. In the course of this study, the ultrastructure of the nuclear events of binary fission in control cells was also studied.During interphase in control cells, the micronucleus contains randomly distributed clumps of condensed chromatin and microtubular fragments. Throughout mitosis the nuclear envelope remains intact. During micronuclear prophase, cup-shaped microfilamentous structures appear that are filled with condensing chromatin. Microtubules are also present and are parallel to the division axis.

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Stimulated Virus Production in Vinblastine and Cytochalasin-Induced Multinucleate Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067923 ◽

1970 ◽

Vol 28 ◽

pp. 186-187

Author(s):

Krishan Awtar

Keyword(s):

Cell Division ◽

Normal Cell ◽

Virus Production ◽

Multinucleate Cells ◽

Daughter Cells ◽

Cell Divisions ◽

Nuclear Membranes ◽

Division 2 ◽

Vinblastine Sulfate

Exposure of cells to low sublethal but mitosis-arresting doses of vinblastine sulfate (Velban) results in the initial arrest of cells in mitosis followed by their subsequent return to an “interphase“-like stage. A large number of these cells reform their nuclear membranes and form large multimicronucleated cells, some containing as many as 25 or more micronuclei (1). Formation of large multinucleate cells is also caused by cytochalasin, by causing the fusion of daughter cells at the end of an otherwise .normal cell division (2). By the repetition of this process through subsequent cell divisions, large cells with 6 or more nuclei are formed.

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The EGL-13 SOX Domain Transcription Factor Affects the Uterine Cell Lineages in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/165.3.1623 ◽

2003 ◽

Vol 165 (3) ◽

pp. 1623-1628

Author(s):

Hediye Nese Cinar ◽

Keri L Richards ◽

Kavita S Oommen ◽

Anna P Newman

Keyword(s):

Transcription Factor ◽

Cell Division ◽

Caenorhabditis Elegans ◽

Cell Fate ◽

Cell Lineages

Abstract We isolated egl-13 mutants in which the cells of the Caenorhabditis elegans uterus initially appeared to develop normally but then underwent an extra round of cell division. The data suggest that egl-13 is required for maintenance of the cell fate.

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Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

Scientific Reports ◽

10.1038/s41598-020-80141-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tim Liebisch ◽

Armin Drusko ◽

Biena Mathew ◽

Ernst H. K. Stelzer ◽

Sabine C. Fischer ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Division ◽

Cell Fate ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Lineage ◽

Cell Fate Decision ◽

Cell Fate Decisions ◽

Chemical Signalling ◽

Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

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