A homeostatic clock sets daughter centriole size in flies

Centrioles are highly structured organelles whose size is remarkably consistent within any given cell type. New centrioles are born when Polo-like kinase 4 (Plk4) recruits Ana2/STIL and Sas-6 to the side of an existing “mother” centriole. These two proteins then assemble into a cartwheel, which grows outwards to form the structural core of a new daughter. Here, we show that in early Drosophila melanogaster embryos, daughter centrioles grow at a linear rate during early S-phase and abruptly stop growing when they reach their correct size in mid- to late S-phase. Unexpectedly, the cartwheel grows from its proximal end, and Plk4 determines both the rate and period of centriole growth: the more active the centriolar Plk4, the faster centrioles grow, but the faster centriolar Plk4 is inactivated and growth ceases. Thus, Plk4 functions as a homeostatic clock, establishing an inverse relationship between growth rate and period to ensure that daughter centrioles grow to the correct size.

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Daughter centrioles assemble preferentially towards the nuclear envelope in Drosophila syncytial embryos

10.1101/2021.11.17.468935 ◽

2021 ◽

Author(s):

Neil Henry James Cunningham ◽

Imene Bouhlel ◽

Paul Thomas Conduit

Keyword(s):

Nuclear Envelope ◽

Single Mother ◽

S Phase ◽

Animal Cells ◽

Simultaneous Formation ◽

Centriole Duplication ◽

External Cues ◽

Mother Centriole ◽

Pericentriolar Material ◽

Daughter Centriole

Centrosomes are important organisers of microtubules within animal cells. They comprise a pair of centrioles surrounded by the pericentriolar material (PCM), which nucleates and organises the microtubules. To maintain centrosome numbers, centrioles must duplicate once and only once per cell cycle. During S-phase, a single new daughter centriole is built orthogonally on one side of each radially symmetric mother centriole. Mis-regulation of duplication can result in the simultaneous formation of multiple daughter centrioles around a single mother centriole, leading to centrosome amplification, a hallmark of cancer. It remains unclear how a single duplication site is established. It also remains unknown whether this site is pre-defined or randomly positioned around the mother centriole. Here, we show that within Drosophila syncytial embryos daughter centrioles preferentially assemble on the side of the mother facing the nuclear envelope, to which the centrosomes are closely attached. This positional preference is established early during duplication and remains stable throughout daughter centriole assembly, but is lost in centrosomes forced to lose their connection to the nuclear envelope. This shows that non-centrosomal cues influence centriole duplication and raises the possibility that these external cues could help establish a single duplication site.

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Three-dimensional organization of Drosophila melanogaster interphase nuclei. I. Tissue-specific aspects of polytene nuclear architecture.

The Journal of Cell Biology ◽

10.1083/jcb.104.6.1455 ◽

1987 ◽

Vol 104 (6) ◽

pp. 1455-1470 ◽

Cited By ~ 78

Author(s):

M Hochstrasser ◽

J W Sedat

Keyword(s):

Drosophila Melanogaster ◽

Three Dimensional ◽

Nuclear Architecture ◽

Close Packing ◽

Prothoracic Gland ◽

Cell Type ◽

Interphase Chromosome ◽

Tissue Specific ◽

Spatial Domains ◽

Four Levels

Interphase chromosome organization in four different Drosophila melanogaster tissues, covering three to four levels of polyteny, has been analyzed. The results are based primarily on three-dimensional reconstructions from unfixed tissues using a computer-based data collection and modeling system. A characteristic organization of chromosomes in each cell type is observed, independent of polyteny, with some packing motifs common to several or all tissues and others tissue-specific. All chromosomes display a right-handed coiling chirality, despite large differences in size and degree of coiling. Conversely, in each cell type, the heterochromatic centromeric regions have a unique structure, tendency to associate, and intranuclear location. The organization of condensed nucleolar chromatin is also tissue-specific. The tightly coiled prothoracic gland chromosomes are arrayed in a similar fashion to the much larger salivary gland chromosomes described previously, having polarized orientations, nonintertwined spatial domains, and close packing of the arms of each autosome, whereas hindgut and especially the unusually straight midgut chromosomes display striking departures from these regularities. Surprisingly, gut chromosomes often appear to be broken in the centric heterochromatin. Severe deformations of midgut nuclei observed during gut contractions in living larvae may account for their unusual properties. Finally, morphometric measurements of chromosome and nuclear dimensions provide insights into chromosome growth and substructure and also suggest an unexpected parallel with diploid chromatin organization.

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Regulation of the start of DNA replication in Schizosaccharomyces pombe

Journal of Cell Science ◽

10.1242/jcs.112.6.939 ◽

1999 ◽

Vol 112 (6) ◽

pp. 939-946 ◽

Cited By ~ 2

Author(s):

C.R. Carlson ◽

B. Grallert ◽

T. Stokke ◽

E. Boye

Keyword(s):

Cell Cycle ◽

Flow Cytometry ◽

Growth Rate ◽

Schizosaccharomyces Pombe ◽

Growth Rates ◽

Cell Separation ◽

Cell Mass ◽

Nitrogen Sources ◽

S Phase ◽

G1 Phase

Cells of Schizosaccharomyces pombe were grown in minimal medium with different nitrogen sources under steady-state conditions, with doubling times ranging from 2.5 to 14 hours. Flow cytometry and fluorescence microscopy confirmed earlier findings that at rapid growth rates, the G1 phase was short and cell separation occurred at the end of S phase. For some nitrogen sources, the growth rate was greatly decreased, the G1 phase occupied 30–50% of the cell cycle, and cell separation occurred in early G1. In contrast, other nitrogen sources supported low growth rates without any significant increase in G1 duration. The method described allows manipulation of the length of G1 and the relative cell cycle position of S phase in wild-type cells. Cell mass was measured by flow cytometry as scattered light and as protein-associated fluorescence. The extensions of G1 were not related to cell mass at entry into S phase. Our data do not support the hypothesis that the cells must reach a certain fixed, critical mass before entry into S. We suggest that cell mass at the G1/S transition point is variable and determined by a set of molecular parameters. In the present experiments, these parameters were influenced by the different nitrogen sources in a way that was independent of the actual growth rate.

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A New Multiparametric Classification in Lung Cancer Patients - S.M.I.G.

Tumori Journal ◽

10.1177/030089168306900511 ◽

1983 ◽

Vol 69 (5) ◽

pp. 437-443 ◽

Cited By ~ 2

Author(s):

Claudio Modini ◽

Mario Albertucci ◽

Franco Cicconetti ◽

Donatella Tirindelli Danesi ◽

Renzo Cristiani ◽

...

Keyword(s):

Lung Cancer ◽

Growth Rate ◽

Mortality Rate ◽

Cancer Patients ◽

Cell Type ◽

Tnm System ◽

Lung Cancer Patients ◽

The Difference

The classification of bronchogenic carcinoma as a function of the prognosis is still an open field. The evaluation of stage, by use of the TNM system, and histologic cell type is not sufficient to guarantee a correct prognosis. The growth rate of the neoplasm is another important parameter. We propose a classification that takes into account the stage (S), histologic cell type (M), immune status (I) and the growth rate of the primary tumor (G): S.M.I.G. We studied 90 lung cancer patients according to the S.M.I.G. classification and we observed that their prognoses were directly correlated with their S.M.I.G. scores (the higher the score, the higher the 10-month mortality rate). The mortality rates within the first 10 months of follow-up were respectively 0%, 0%, 36.36%, 68%, 90.9% for the 5 groups obtained by S.M.I.G. The difference is statistically significant (P < 0.0075) and there is a linear correlation between the mortality rate and the score assigned to each group (R = 0.943; P < 0.05). The S.M.I.G. classification can predict the prognosis more efficiently than the usual classification (TNM) and histological cell type.

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BCL-2 Expression Correlates With Lower Proliferative Activity in the Intermediate- and High-Grade Non-Hodgkin's Lymphomas: An Eastern Cooperative Oncology Group and Southwest Oncology Group Cooperative Laboratory Study

Blood ◽

10.1182/blood.v91.4.1391 ◽

1998 ◽

Vol 91 (4) ◽

pp. 1391-1398 ◽

Cited By ~ 32

Author(s):

Jane N. Winter ◽

Janet Andersen ◽

John C. Reed ◽

Stanislaw Krajewski ◽

Daina Variakojis ◽

...

Keyword(s):

Cell Cycle ◽

Proliferative Activity ◽

Inverse Relationship ◽

Eastern Cooperative Oncology Group ◽

Flow Cytometric Analysis ◽

S Phase ◽

Breakpoint Region ◽

High Grade ◽

Oncology Group ◽

Hodgkin's Lymphomas

Abstract An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAXexpression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction). BCL-2 expression was inversely associated with proliferative activity (P = .001; n = 41), but there was no association between staining for Bax and %S-phase. Ploidy was not associated with either BCL-2 or BAX expression. The t(14;18) was detected in 21 of the 54 cases in which PCR-amplifiable DNA was recovered; 20 of these occurred at the major breakpoint region and 1 at the minor breakpoint region. High levels of BCL-2 orBAX expression occurred independently of t(14;18). There was no association between t(14;18) and either ploidy or proliferative activity. The inverse relationship between BCL-2 expression and proliferative activity in the intermediate- and high-grade NHLs is consistent with recent studies suggesting that Bcl-2 both retards entry into the cell cycle and inhibits apoptosis.

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Evolution of reduced pre-adult viability and larval growth rate in laboratory populations of Drosophila melanogaster selected for shorter development time

Genetics Research ◽

10.1017/s0016672300004754 ◽

2000 ◽

Vol 76 (3) ◽

pp. 249-259 ◽

Cited By ~ 45

Author(s):

N. G. PRASAD ◽

MALLIKARJUN SHAKARAD ◽

VISHAL M. GOHIL ◽

V. SHEEBA ◽

M. RAJAMANI ◽

...

Keyword(s):

Growth Rate ◽

Drosophila Melanogaster ◽

Development Time ◽

Larval Growth ◽

Dry Weight ◽

Relative Reduction ◽

Larval Growth Rate ◽

Laboratory Populations ◽

The Difference ◽

Faster Development

Four large (n > 1000) populations of Drosophila melanogaster, derived from control populations maintained on a 3 week discrete generation cycle, were subjected to selection for fast development and early reproduction. Egg to eclosion survivorship and development time and dry weight at eclosion were monitored every 10 generations. Over 70 generations of selection, development time in the selected populations decreased by approximately 36 h relative to controls, a 20% decline. The difference in male and female development time was also reduced in the selected populations. Flies from the selected populations were increasingly lighter at eclosion than controls, with the reduction in dry weight at eclosion over 70 generations of selection being approximately 45% in males and 39% in females. Larval growth rate (dry weight at eclosion/development time) was also reduced in the selected lines over 70 generations, relative to controls, by approximately 32% in males and 24% in females. However, part of this relative reduction was due to an increase in growth rate of the controls populations, presumably an expression of adaptation to conditions in our laboratory. After 50 generations of selection had elapsed, a considerable and increasing pre- adult viability cost to faster development became apparent, with viability in the selected populations being about 22% less than that of controls at generation 70 of selection.

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Growth rate and longevity in Drosophila melanogaster and Tribolium castaneum

Nature ◽

10.1038/266624a0 ◽

1977 ◽

Vol 266 (5603) ◽

pp. 624-625 ◽

Cited By ~ 17

Author(s):

F. A. LINTS ◽

M. H. SOLIMAN

Keyword(s):

Growth Rate ◽

Drosophila Melanogaster ◽

Tribolium Castaneum

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HUMAN MONOCYTES AND MACROPHAGES

The Journal of Cell Biology ◽

10.1083/jcb.46.1.97 ◽

1970 ◽

Vol 46 (1) ◽

pp. 97-105 ◽

Cited By ~ 47

Author(s):

J. M. Hanifin ◽

M. J. Cline

Keyword(s):

Lymphocyte Transformation ◽

S Phase ◽

Mononuclear Phagocytes ◽

Human Monocytes ◽

Cell Type ◽

Morphological Transformation ◽

Lymphocyte Cultures ◽

Monocytes And Macrophages ◽

Lymphocyte Dna Synthesis ◽

Human Monocytes And Macrophages

PPD-sensitized monocytes and macrophages from tuberculin-positive subjects are both capable of inducing blastogenic transformation of autologous lymphocytes. Incorporation of thymidine-3H and morphological transformation were always greater in lymphocyte cultures containing macrophages than in those containing monocytes. More lymphocytes entered the first detectable S phase in cultures containing macrophages. Lymphocyte DNA synthesis occurred as early as 40 hr of culture and always in cells in contact with mononuclear phagocytes. By 120–144 hr, many transformed lymphocytes were free in suspension; at the same time, the "immunological cluster" had increased greatly in size and contained transformed and untransformed lymphocytes. The greater effectiveness of macrophages at induction of lymphocyte transformation may be related to the efficiency of this cell type at trapping antigen and its effectiveness at making contact with and binding lymphocytes.

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