scholarly journals PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo

2014 ◽  
Vol 205 (4) ◽  
pp. 447-455 ◽  
Author(s):  
Laura Benkemoun ◽  
Catherine Descoteaux ◽  
Nicolas T. Chartier ◽  
Lionel Pintard ◽  
Jean-Claude Labbé
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Cycle Duration ◽  
Cell Stage ◽  
C Elegans ◽  
Stage Embryo ◽  
Regulation Of Cell Cycle

Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division.

scholarly journals JAK/STAT pathway promotes Drosophila neuroblast proliferation via the direct CycE regulation

2020 ◽  
Author(s):  
Lijuan Du ◽  
Jian Wang
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Stat Signaling ◽  
Stat Pathway

AbstractHow neural stem cells regulate their proliferative potential and lineage diversity is a central problem in developmental neurobiology. Drosophila Mushroom bodies (MBs), centers of olfactory learning and memory, are generated by a specific set of neuroblasts (Nbs) that are born in the embryonic stage and continuously proliferate till the end of the pupal stage. Although MB presents an excellent model for studying neural stem cell proliferation, the genetic and molecular mechanisms that control the unique proliferative characteristics of the MB Nbs are largely unknown. Further, the signaling cues controlling cell cycle regulators to promote cell cycle progression in MB Nbs remain poorly understood. Here, we report that JAK/STAT signaling pathway is required for the proliferation activity and maintenance of MB Nbs. Loss of JAK/STAT activity severely reduces the later-born MB neuron types and leads to premature neuroblast termination, which can be rescued by tissue-specific overexpression of CycE and diap1. Higher JAK/STAT pathway activity in MB results in more neurons, without producing supernumerary Nbs. Furthermore, we show that JAK/STAT signaling effector Stat92E directly regulates CycE transcription in MB Nbs. Finally, MB Nb clones of loss or excess CycE phenocopy those of decreased or increased JAK/STAT signaling pathway activities. We conclude that JAK/STAT signaling controls MB Nb proliferative activity through directly regulating CycE expression to control cell cycle progression.

scholarly journals Probing and manipulating embryogenesis via nanoscale thermometry and temperature control

2020 ◽  
Vol 117 (26) ◽  
pp. 14636-14641 ◽  
Author(s):  
Joonhee Choi ◽  
Hengyun Zhou ◽  
Renate Landig ◽  
Hai-Yin Wu ◽  
Xiaofei Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Communication ◽  
Cycle Duration ◽  
Cell Stage ◽  
C Elegans ◽  
Local Perturbations ◽  
Cell Division Timing ◽  
Nanoscale Thermometry

Understanding the coordination of cell-division timing is one of the outstanding questions in the field of developmental biology. One active control parameter of the cell-cycle duration is temperature, as it can accelerate or decelerate the rate of biochemical reactions. However, controlled experiments at the cellular scale are challenging, due to the limited availability of biocompatible temperature sensors, as well as the lack of practical methods to systematically control local temperatures and cellular dynamics. Here, we demonstrate a method to probe and control the cell-division timing inCaenorhabditis elegansembryos using a combination of local laser heating and nanoscale thermometry. Local infrared laser illumination produces a temperature gradient across the embryo, which is precisely measured by in vivo nanoscale thermometry using quantum defects in nanodiamonds. These techniques enable selective, controlled acceleration of the cell divisions, even enabling an inversion of division order at the two-cell stage. Our data suggest that the cell-cycle timing asynchrony of the early embryonic development inC. elegansis determined independently by individual cells rather than via cell-to-cell communication. Our method can be used to control the development of multicellular organisms and to provide insights into the regulation of cell-division timings as a consequence of local perturbations.

scholarly journals Alternative splicing regulation of cell cycle genes by SPF45/SR140/CHERP complex controls cell proliferation

RNA ◽  
2021 ◽  
pp. rna.078935.121
Author(s):  
Elena Martin ◽  
Claudia Vivori ◽  
Malgorzata Rogalska ◽  
Jorge Herrero ◽  
Juan Valcarcel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Alternative Splicing ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Splicing Factors ◽  
Splicing Regulation ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Regulation Of Cell Cycle

The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140 and CHERP form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulate the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.

scholarly journals Reducing inositol lipid hydrolysis, Ins(1,4,5)P3 receptor availability, or Ca2+ gradients lengthens the duration of the cell cycle in Xenopus laevis blastomeres.

1992 ◽  
Vol 116 (1) ◽  
pp. 147-156 ◽  
Author(s):  
J K Han ◽  
K Fukami ◽  
R Nuccitelli
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Xenopus Laevis ◽  
Mitotic Cell ◽  
Embryonic Cell ◽  
Cycle Duration ◽  
Cell Stage ◽  
Stage Embryo ◽  
Rate Of Hydrolysis ◽  
Xenopus Laevis Embryos

We have microinjected a mAb specifically directed to phosphatidylinositol 4,5-bisphosphate (PIP2) into one blastomere of two-cell stage Xenopus laevis embryos. This antibody binds to endogenous PIP2 and reduces its rate of hydrolysis by phospholipase C. Antibody-injected blastomeres undergo partial or complete arrest of the cell cycle whereas the uninjected sister blastomeres divided normally. Since PIP2 hydrolysis normally produces diacylglycerol (DG) and inositol 1,4,5-triphosphate (Ins[1,4,5]P3), we attempted to measure changes in the levels of DG following stimulation of PIP2 hydrolysis in antibody-injected oocytes. The total amount of DG in antibody-injected oocytes was significantly reduced compared to that of water-injected ones following stimulation by either acetylcholine or progesterone indicating that the antibody does indeed suppress PIP2 hydrolysis. We also found that the PIP2 antibodies greatly reduced the amount of intracellular Ca2+ released in the egg cortex during egg activation. As an indirect test for Ins(1,4,5)P3 involvement in the cell cycle we injected heparin which competes with Ins(1,4,5)P3 for binding to its receptor, and thus inhibits Ins(1,4,5)P3-induced Ca2+ release. Microinjection of heparin into one blastomere of the two-cell stage embryo caused partial or complete arrest of the cell cycle depending upon the concentration of heparin injected. We further investigated the effect of reducing any [Ca2+]i gradients by microinjecting dibromo-BAPTA into the blastomere. Dibromo-BAPTA injection completely blocked mitotic cell division when a final concentration of 1.5 mM was used. These results suggest that PIP2 turnover as well as second messenger activity influence cell cycle duration during embryonic cell division in frogs.

scholarly journals Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Open Biology ◽  
2013 ◽  
Vol 3 (8) ◽  
pp. 130083 ◽  
Author(s):  
Anna Noatynska ◽  
Nicolas Tavernier ◽  
Monica Gotta ◽  
Lionel Pintard
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Control Cell ◽  
Model Organisms ◽  
Cycle Progression

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

scholarly journals Analysis of Endothelial-to-Haematopoietic Transition at the Single Cell Level identifies Cell Cycle Regulation as a Driver of Differentiation

2020 ◽  
Author(s):  
Giovanni Canu ◽  
Emmanouil Athanasiadis ◽  
Rodrigo A. Grandy ◽  
Jose Garcia-Bernardo ◽  
Paulina M. Strzelecka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Single Cell ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Time Window ◽  
Control Cell ◽  
Quiescent State ◽  
Differentiation Potential

ABSTRACTHaematopoietic stem cells (HSC) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. In this study, we took advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrated that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. Therefore, we propose a direct link between the molecular machineries that control cell cycle progression and EHT.

scholarly journals Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases

2002 ◽  
Vol 158 (3) ◽  
pp. 435-444 ◽  
Author(s):  
Eric Rutledge ◽  
Jerod Denton ◽  
Kevin Strange
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Cell Swelling ◽  
Phosphatase Inhibitors ◽  
C Elegans ◽  
Physiological Processes ◽  
Cycle Dependent ◽  
Regulation Of Cell Cycle

ClC voltage-gated anion channels have been identified in bacteria, yeast, plants, and animals. The biophysical and structural properties of ClCs have been studied extensively, but relatively little is known about their precise physiological functions. Furthermore, virtually nothing is known about the signaling pathways and molecular mechanisms that regulate channel activity. The nematode Caenorhabditis elegans provides significant experimental advantages for characterizing ion channel function and regulation. We have shown previously that the ClC Cl− channel homologue CLH-3 is expressed in C. elegans oocytes, and that it is activated during meiotic maturation and by cell swelling. We demonstrate here that depletion of intracellular ATP or removal of Mg2+, experimental maneuvers that inhibit kinase function, constitutively activate CLH-3. Maturation- and swelling-induced channel activation are inhibited by type 1 serine/threonine phosphatase inhibitors. RNA interference studies demonstrated that the type 1 protein phosphatases CeGLC-7α and β, both of which play essential regulatory roles in mitotic and meiotic cell cycle events, mediate CLH-3 activation. We have suggested previously that CLH-3 and mammalian ClC-2 are orthologues that play important roles in heterologous cell–cell interactions, intercellular communication, and regulation of cell cycle–dependent physiological processes. Consistent with this hypothesis, we show that heterologously expressed rat ClC-2 is also activated by serine/threonine dephosphorylation, suggesting that the two channels have common regulatory mechanisms.

Cell-cycle-dependent telomere elongation by telomerase in budding yeast

2011 ◽  
Vol 31 (3) ◽  
pp. 169-177
Author(s):  
Shang Li
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Budding Yeast ◽  
Telomere Elongation ◽  
The Stability ◽  
Cycle Dependent ◽  
Linear Chromosomes ◽  
Telomere Chromatin

Telomeres are essential for the stability and complete replication of linear chromosomes. Telomere elongation by telomerase counteracts the telomere shortening due to the incomplete replication of chromosome ends by DNA polymerase. Telomere elongation is cell-cycle-regulated and coupled to DNA replication during S-phase. However, the molecular mechanisms that underlie such cell-cycle-dependent telomere elongation by telomerase remain largely unknown. Several aspects of telomere replication in budding yeast, including the modulation of telomere chromatin structure, telomere end processing, recruitment of telomere-binding proteins and telomerase complex to telomere as well as the coupling of DNA replication to telomere elongation during cell cycle progression will be discussed, and the potential roles of Cdk (cyclin-dependent kinase) in these processes will be illustrated.

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