scholarly journals ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification

2020 ◽  
Vol 98 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Connor O’Sullivan ◽  
Philip E.B. Nickerson ◽  
Oliver Krupke ◽  
Jennifer Christie ◽  
Li-Li Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cell Fate Specification ◽  
Retinal Progenitor Cells ◽  
Cycle Progression ◽  
Fate Specification ◽  
Retinal Progenitor

During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3′-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2–FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal 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.

scholarly journals Loss of Nance-Horan Syndrome b (nhsb) prevents expansion growth of retinal progenitor cells by selective up-regulation of Δ113p53

2019 ◽  
Author(s):  
Paul J. Vorster ◽  
John Ojumu ◽  
Amanda J. G. Dickinson ◽  
Gregory S. Walsh
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Retinal Progenitor Cells ◽  
Cycle Progression ◽  
Retinal Progenitor ◽  
Eye Size ◽  
Regulation Of Cell Cycle

AbstractThe regulation of cell cycle progression and differentiation in retinal progenitor cells is a fundamental feature controlling organ size of the eye in vertebrates. Nance-Horan Syndrome (NHS) is a rare X-linked disorder caused by mutations in the NHS gene. Dysmorphic features of NHS include severe congenital cataracts, micropthalmia, facial dysmorphisms, and visual impairment. In this study we report an evolutionarily conserved role for NHS in vertebrate retinogenesis. Loss of function of nhs leads to small eye size in both zebrafish and Xenopus tropicalis, marked by reduced proliferation but not cell death. Transcriptome analysis of nhs morphant zebrafish eyes revealed a marked upregulation in Δ113p53, an isoform of p53, concomitant with a selective upregulation of p53 responsive genes that inhibit cell cycle progression but not apoptosis. Our data supports a model where Nhs is a negative regulator of Δ113p53 expression and exerts its function through regulation of the p53 pathway to promote expansive growth of retinal progenitor cells prior to differentiation.

scholarly journals Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye

2016 ◽  
Vol 419 (2) ◽  
pp. 336-347 ◽  
Author(s):  
Jin Young Kim ◽  
Raehee Park ◽  
Jin Hwan J. Lee ◽  
Jinyeon Shin ◽  
Jenna Nickas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Retinal Progenitor Cell ◽  
Retinal Progenitor

scholarly journals Defective Gene Expression, S Phase Progression, and Maturation during Hematopoiesis in E2F1/E2F2 Mutant Mice

2003 ◽  
Vol 23 (10) ◽  
pp. 3607-3622 ◽  
Author(s):  
Feng X. Li ◽  
Jing W. Zhu ◽  
Christopher J. Hogan ◽  
James DeGregori
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
S Phase ◽  
Mutant Mice ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cycle Progression ◽  
Phase Progression

ABSTRACT E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control. We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell lineages. E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia. Importantly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from impeded S phase progression in hematopoietic progenitor cells. During DKO B-cell maturation, differentiation beyond the large pre-BII-cell stage is defective, presumably due to failed cell cycle exit, and the cells undergo apoptosis. However, apoptosis appears to be the consequence of failed maturation, not the cause. Despite the accumulation of hematopoietic progenitor cells in S phase, the combined loss of E2F1 and E2F2 results in significantly decreased expression and activities of several E2F target genes including cyclin A2. Our results indicate specific roles for E2F1 and E2F2 in the induction of E2F target genes, which contribute to efficient expansion and maturation of hematopoietic progenitor cells. Thus, E2F1 and E2F2 play essential and redundant roles in the proper coordination of cell cycle progression with differentiation which is necessary for efficient hematopoiesis.

scholarly journals The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

2021 ◽  
Vol 22 (11) ◽  
pp. 5483
Author(s):  
Luisa F. Bustamante-Jaramillo ◽  
Celia Ramos ◽  
Cristina Martín-Castellanos
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Cell Cycle Progression ◽  
Nuclear Architecture ◽  
Strand Break ◽  
Spindle Pole ◽  
S Phase ◽  
Cycle Progression ◽  
Single Wave ◽  
Phase Progression

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.

scholarly journals Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 205
Author(s):  
Su-Jin Jeong ◽  
Jeong-Wook Choi ◽  
Min-Kyeong Lee ◽  
Youn-Hee Choi ◽  
Taek-Jeong Nam
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Crude Protein ◽  
Cell Cycle Progression ◽  
Intestinal Epithelial Cells ◽  
Mapk Signaling ◽  
S Phase ◽  
Intestinal Epithelial ◽  
Cycle Progression

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

scholarly journals Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression

2020 ◽  
Vol 8 ◽  
Author(s):  
Deqin Kong ◽  
Rui Liu ◽  
Jiangzheng Liu ◽  
Qingbiao Zhou ◽  
Jiaxin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Cycle Progression ◽  
Hepatocellular Carcinoma Cells ◽  
G2 Phase ◽  
Human Hepatocellular Carcinoma Cells

Cubic membranes (CMs) represent unique biological membrane structures with highly curved three-dimensional periodic minimal surfaces, which have been observed in a wide range of cell types and organelles under various stress conditions (e. g., starvation, virus-infection, and oxidation). However, there are few reports on the biological roles of CMs, especially their roles in cell cycle. Hence, we established a stable cell population of human hepatocellular carcinoma cells (HepG2) of 100% S phase by thymidine treatment, and determined certain parameters in G2 phase released from S phase. Then we found a close relationship between CMs formation and cell cycle, and an increase in reactive oxygen species (ROS) and mitochondrial function. After the synchronization of HepG2 cells were induced, CMs were observed through transmission electron microscope in G2 phase but not in G1, S and M phase. Moreover, the increased ATP production, mitochondrial and intracellular ROS levels were also present in G2 phase, which demonstrated a positive correlation with CMs formation by Pearson correlation analysis. This study suggests that CMs may act as an antioxidant structure in response to mitochondria-derived ROS during G2 phase and thus participate in cell cycle progression.

p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3593-3605 ◽  
Author(s):  
M.A. Dyer ◽  
C.L. Cepko
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Kinase Inhibitor ◽  
Retinal Development ◽  
Cell Types ◽  
Cell Cycle Exit ◽  
Retinal Progenitor Cells ◽  
Mouse Development ◽  
Retinal Progenitor ◽  
Cyclin Kinase Inhibitor

A precise balance between proliferation and differentiation must be maintained during retinal development to obtain the correct proportion of each of the seven cell types found in the adult tissue. Cyclin kinase inhibitors can regulate cell cycle exit coincident with induction of differentiation programs during development. We have found that the p57(Kip2) cyclin kinase inhibitor is upregulated during G(1)/G(0) in a subset of retinal progenitor cells exiting the cell cycle between embryonic day 14.5 and 16.5 of mouse development. Retroviral mediated overexpression of p57(Kip2) in embryonic retinal progenitor cells led to premature cell cycle exit. Retinae from mice lacking p57(Kip2) exhibited inappropriate S-phase entry and apoptotic nuclei were found in the region where p57(Kip2) is normally expressed. Apoptosis precisely compensated for the inappropriate proliferation in the p57(Kip2)-deficient retinae to preserve the correct proportion of the major retinal cell types. Postnatally, p57(Kip2) was found to be expressed in a novel subpopulation of amacrine interneurons. At this stage, p57(Kip2)did not regulate proliferation. However, perhaps reflecting its role during this late stage of development, animals lacking p57(Kip2) showed an alteration in amacrine subpopulations. p57(Kip2) is the first gene to be implicated as a regulator of amacrine subtype/subpopulation development. Consequently, we propose that p57(Kip2) has two roles during retinal development, acting first as a cyclin kinase inhibitor in mitotic progenitor cells, and then playing a distinct role in neuronal differentiation.

scholarly journals Effects of Guanine Nucleotide Depletion on Cell Cycle Progression in Human T Lymphocytes

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2896-2904 ◽  
Author(s):  
Josée Laliberté ◽  
Ann Yee ◽  
Yue Xiong ◽  
Beverly S. Mitchell
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Guanine Nucleotides ◽  
Erythroid Cell ◽  
Guanine Nucleotide ◽  
Cycle Progression ◽  
Human T Lymphocytes

Depletion of guanine nucleotide pools after inhibition of inosine monophosphate dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cells in G1 and has been shown to induce the differentiation of cultured myeloid and erythroid cell lines, as well as chronic granulocytic leukemic cells after blast transformation. Inhibitors of IMPDH are also highly effective as immunosuppressive agents. The mechanism underlying these pleiotropic effects of depletion of guanine nucleotides is unknown. We have examined the effects of mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression of activated normal human T lymphocytes. MPA treatment resulted in the inhibition of pRb phosphorylation and cell entry into S phase. The expression of cyclin D3, a major component of the cyclin-dependent kinase (CDK) activity required for pRb phosphorylation, was completely abrogated by MPA treatment of T cells activated by interleukin-2 (IL-2) and leucoagglutinin (PHA-L), whereas the expression of cyclin D2, CDK6, and CDK4 was more mildly attenuated. The direct kinase activity of a complex immunoprecipitated with anti-CDK6 antibody was also inhibited. In addition, MPA prevented the IL-2–induced elimination of p27Kip1, a CDK inhibitor, and resulted in the retention of high levels of p27Kip1 in IL-2/PHA-L–treated T cells bound to CDK2. These results indicate that inhibition of the de novo synthesis of guanine nucleotides blocks the transition of normal peripheral blood T lymphocytes from G0 to S phase in early- to mid-G1 and that this cell cycle arrest results from inhibition of the induction of cyclin D/CDK6 kinase and the elimination of p27Kip1 inhibitory activity.

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