scholarly journals Co-ordination of cell cycle and differentiation in the developing nervous system

2012 ◽  
Vol 444 (3) ◽  
pp. 375-382 ◽  
Author(s):  
Christopher Hindley ◽  
Anna Philpott
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Embryonic Development ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Control Cell ◽  
Cell Cycle Regulators ◽  
Cyclin Dependent Kinases ◽  
Proliferation And Differentiation ◽  
Developing Nervous System

During embryonic development, cells must divide to produce appropriate numbers, but later must exit the cell cycle to allow differentiation. How these processes of proliferation and differentiation are co-ordinated during embryonic development has been poorly understood until recently. However, a number of studies have now given an insight into how the cell cycle machinery, including cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle regulators directly influence mechanisms that control cell fate and differentiation. Conversely, examples are emerging of transcriptional regulators that are better known for their role in driving the differentiated phenotype, which also play complementary roles in controlling cell cycle progression. The present review will summarise our current understanding of the mechanisms co-ordinating the cell cycle and differentiation in the developing nervous system, where these links have been, perhaps, most extensively studied.

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.

Protein kinase C involvement in cell cycle modulation

2014 ◽  
Vol 42 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Alessandro Poli ◽  
Sara Mongiorgi ◽  
Lucio Cocco ◽  
Matilde Y. Follo
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Models ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Cell Cycle Modulation ◽  
Proliferation And Differentiation

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.

scholarly journals Identification of MoKA, a Novel F-Box Protein That Modulates Krüppel-Like Transcription Factor 7 Activity

2004 ◽  
Vol 24 (3) ◽  
pp. 1058-1069 ◽  
Author(s):  
Silvia Smaldone ◽  
Friedrich Laub ◽  
Cindy Else ◽  
Cecilia Dragomir ◽  
Francesco Ramirez
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Transcription Factor ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Direct Interaction ◽  
Proximal Promoter ◽  
F Box Protein ◽  
Developing Nervous System

ABSTRACT KLF7, a member of the Krüppel-like transcription factor family, is believed to regulate neurogenesis and cell cycle progression. Here, a yeast two-hybrid screen for KLF7 cofactors in the developing nervous system identified a novel 140-kDa protein named MoKA, for modulator of KLF7 activity. Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator, and in situ hybridizations identified the developing nervous system and the adult testes as two sites of MoKA and Klf7 coexpression. Chromatin immunoprecipitation experiments demonstrated KLF7 binding to the p21WAF1/Cip1 gene while transient transfection assays documented KLF7 stimulation of the p21WAF1/Cip1 proximal promoter. Additional tests revealed that distinct structural motifs of MoKA direct interaction with KLF7 and shuttling between the nucleus and cytoplasm of asynchronously cycling cells. Altogether, our results strongly suggest that MoKA and KLF7 interact functionally to regulate gene expression during cell differentiation and identify the cell cycle regulator p21WAF1/Cip1 as one of the targeted genes.

scholarly journals Surface sensing stimulates cellular differentiation inCaulobacter crescentus

2020 ◽  
Vol 117 (30) ◽  
pp. 17984-17991 ◽  
Author(s):  
Rhett A. Snyder ◽  
Courtney K. Ellison ◽  
Geoffrey B. Severin ◽  
Gregory B. Whitfield ◽  
Christopher M. Waters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cellular Differentiation ◽  
Cell Cycle Progression ◽  
Caulobacter Crescentus ◽  
Control Cell ◽  
Chromosome Replication ◽  
Cycle Progression ◽  
Surface Sensing ◽  
Surface Contact

Cellular differentiation is a fundamental strategy used by cells to generate specialized functions at specific stages of development. The bacteriumCaulobacter crescentusemploys a specialized dimorphic life cycle consisting of two differentiated cell types. How environmental cues, including mechanical inputs such as contact with a surface, regulate this cell cycle remain unclear. Here, we find that surface sensing by the physical perturbation of retracting extracellular pilus filaments accelerates cell-cycle progression and cellular differentiation. We show that physical obstruction of dynamic pilus activity by chemical perturbation or by a mutation in the outer-membrane pilus secretin CpaC stimulates early initiation of chromosome replication. In addition, we find that surface contact stimulates cell-cycle progression by demonstrating that surface-stimulated cells initiate early chromosome replication to the same extent as planktonic cells with obstructed pilus activity. Finally, we show that obstruction of pilus retraction stimulates the synthesis of the cell-cycle regulator cyclic diguanylate monophosphate (c-di-GMP) through changes in the activity and localization of two key regulatory histidine kinases that control cell fate and differentiation. Together, these results demonstrate that surface contact and sensing by alterations in pilus activity stimulateC. crescentusto bypass its developmentally programmed temporal delay in cell differentiation to more quickly adapt to a surface-associated lifestyle.

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 CUL-4A Is Critical for Early Embryonic Development

2002 ◽  
Vol 22 (14) ◽  
pp. 4997-5005 ◽  
Author(s):  
Binghui Li ◽  
Joseph C. Ruiz ◽  
Kristin T. Chun
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Cell Cycle Progression ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Early Embryonic Development ◽  
Cell Cycle Regulators ◽  
Mendelian Genetics ◽  
Physiologic Function ◽  
Core Components

ABSTRACT Ubiquitin-mediated degradation targets cell cycle regulators for proteolysis. Much of the ubiquitin pathway's substrate specificity is conferred by E3 ubiquitin ligases, and cullins are core components of some E3s. CUL-4A encodes one of six mammalian cullins and is amplified and/or overexpressed in breast cancer, which suggests a role in regulating cell cycle progression. To examine CUL-4A's physiologic function, we generated a CUL-4A deletion mutation in mice. No viable CUL-4A −/− pups and no homozygous mutant embryos as early as 7.5 days postcoitum (dpc) were recovered. However, CUL-4A −/− blastocysts are viable, hatch, form an inner cell mass and trophectoderm, and implant (roughly 4.5 dpc), indicating that CUL-4A −/− embryos die between 4.5 and 7.5 dpc. Despite 87% similarity between the Cul-4A and Cul-4B cullins, the CUL-4A −/− lethal phenotype indicates that CUL-4A has one or more distinct function(s). Surprisingly, 44% fewer heterozygous pups were recovered than expected by Mendelian genetics, indicating that many heterozygous embryos also die during gestation due to haploinsufficiency. Taken together, our findings indicate that appropriate CUL-4A expression is critical for early embryonic development.

Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3713-3721 ◽  
Author(s):  
K. Weigmann ◽  
C.F. Lehner
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Cell Fate ◽  
Mother Cell ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cell Fate Specification ◽  
Cycle Progression ◽  
Fate Specification ◽  
Ganglion Mother Cell

The correct specification of defined neurons in the Drosophila central nervous system is dependent on even-skipped. During CNS development, even-skipped expression starts in the ganglion mother cell resulting from the first asymmetric division of neuroblast NB 1–1. This first division of NB 1–1 (and of the other early neuroblasts as well) is temporally controlled by the transcriptional regulation of string expression, which we have manipulated experimentally, even-skipped expression still occurs if the first neuroblast division is delayed, but not if the division is prohibited. Moreover, even-skipped expression is also dependent on progression through S phase which follows immediately after the first division. However, cytokinesis during the first NB division is not required for even-skipped expression as revealed by observations in pebble mutant embryos. Our results demonstrate therefore that even-skipped expression is coupled to cell cycle progression, presumably in order to prevent a premature activation of expression by a positive regulator which is produced already in the neuroblast during G2 and segregated asymmetrically into the ganglion mother cell during mitosis.

Cell cycle and cell fate in the developing nervous system: the role of CDC25B phosphatase

2014 ◽  
Vol 359 (1) ◽  
pp. 201-213 ◽  
Author(s):  
Eric Agius ◽  
Sophie Bel-Vialar ◽  
Frédéric Bonnet ◽  
Fabienne Pituello
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Cell Fate ◽  
Developing Nervous System

scholarly journals Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system

2011 ◽  
Vol 193 (2) ◽  
pp. 397-407 ◽  
Author(s):  
Céline Caillava ◽  
Renaud Vandenbosch ◽  
Beata Jablonska ◽  
Cyrille Deboux ◽  
Giulia Spigoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Cycle Progression ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Proliferation And Differentiation ◽  
Demyelinating Lesions ◽  
Underlying Mechanisms

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2−/− mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin.

scholarly journals Dilution and titration of cell-cycle regulators may control cell size in budding yeast

2018 ◽  
Author(s):  
Frank S. Heldt ◽  
Reece Lunstone ◽  
John J. Tyson ◽  
Béla Novák
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Control Cell ◽  
Gene Copy Number ◽  
Size Control ◽  
Gene Copy ◽  
Cell Cycle Regulators

AbstractThe size of a cell sets the scale for all biochemical processes within it, thereby affecting cellular fitness and survival. Hence, cell size needs to be kept within certain limits and relatively constant over multiple generations. However, how cells measure their size and use this information to regulate growth and division remains controversial. Here, we present two mechanistic mathematical models of the budding yeast (S. cerevisiae) cell cycle to investigate competing hypotheses on size control: inhibitor dilution and titration of nuclear sites. Our results suggest that an inhibitor-dilution mechanism, in which cell growth dilutes the transcriptional inhibitor Whi5 against the constant activator Cln3, can facilitate size homeostasis. This is achieved by utilising a positive feedback loop to establish a fixed size threshold for the START transition, which efficiently couples cell growth to cell cycle progression. Yet, we show that inhibitor dilution cannot reproduce the size of mutants that alter the cell’s overall ploidy and WHI5 gene copy number. By contrast, size control through titration of Cln3 against a constant number of genomic binding sites for the transcription factor SBF recapitulates both size homeostasis and the size of these mutant strains. Moreover, this model produces an imperfect ‘sizer’ behaviour in G1 and a ‘timer’ in S/G2/M, which combine to yield an ‘adder’ over the whole cell cycle; an observation recently made in experiments. Hence, our model connects these phenomenological data with the molecular details of the cell cycle, providing a systems-level perspective of budding yeast size control.

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