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Results for “Resting Phase, Cell Cycle”

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At least 343 records · Page 19Linked to original sources

PubMed2000

Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study.

PURPOSE: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation METHODS AND MATERIALS: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. RESULTS: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p < 0.001) following 28 Gy and following 20 Gy (p < 0.05) in a single dose. Endothelial cell loss was the same for single- and split-dose schedules. Progressive endothelial cell loss produced vessel collapse and acellular vessel strands. Endothelial cells were in the G(0) phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. CONCLUSION: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density.

Animals↗

PubMed1996

Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts.

Reversible growth arrest has been characterised for enhanced expression of a set of genes called gas (growth arrest specific). gas6 product (Gas6) is a secreted protein that was identified as the ligand for the tyrosine kinase receptor Axl. Here we report that Gas6 is able to induce cell cycle division entry in serum starved NIH3T3 cells. This mitogenic activity of Gas6 strictly correlates with its ability to interact with NIH3T3 endogenous Axl receptor since it can be abolished by soluble Axl extracellular domain and activates both Axl intrinsic kinase activity and the downstream MAPK pathway. Moreover when ectopic Axl overexpression is performed by microinjection in serum starved NIH3T3 cells, addition of a non mitogenic level of Gas6 induces selective entry into S phase in Axl overexpressing cells. Interestingly, Axl overexpression per se is not able to induce S phase entry. Finally we present evidences indicating that Gas6 is able to protect serum starved NIH3T3 cells from cell death by apoptosis as induced by complete growth factor depletion. The reported survival activity seems to be independent of Gas6 mitogenic activity, thus implicating a double and separable activity for Gas6 during growth arrest.

3T3 Cells↗

PubMed1994

The nuclear position of pericentromeric DNA of chromosome 11 appears to be random in G0 and non-random in G1 human lymphocytes.

The nuclear topography of pericentromeric DNA of chromosome 11 was analyzed in G0 (nonstimulated) and G1 [phytohemagglutinin (PHA) stimulated] human lymphocytes by confocal microscopy. In addition to the nuclear center, the centrosome was used as a second point of reference in the three-dimensional (3D) analysis. Pericentromeric DNA of chromosome 11 and the centrosome were labeled using a combination of fluorescent in situ hybridization (FISH) and immunofluorescence. To preserve the 3D morphology of the cells, these techniques were performed on whole cells in suspension. Three-dimensional images of the cells were analyzed with a recently developed 3D software program (Interactive Measurement of Axes and Positioning in 3 Dimensions). The distribution of the chromosome 11 centromeres appeared to be random during the G0 stage but clearly non-random during the G1 stage, when the nuclear center was used as a reference point. Further statistical analysis of the G1 cells revealed that the centromeres were randomly distributed in a shell underlying the nuclear membrane. A topographical relationship between the centrosome and the centromeres appeared to be absent during the G0 and G1 stages of the cell cycle.

Cell Nucleus↗

PubMed1999

Inhibition of caspases rescues brown adipocytes from apoptosis downregulating BCL-XS and upregulating BCL-2 gene expression.

Serum deprivation of the immortalized brown adipocyte cell line resulted in growth arrest in G0/G1 phases of the cell cycle and apoptosis, as detected by DNA laddering, nuclei condensation and fragmentation, and an increase in the percentage of hypodiploid cells. In addition, apoptosis in these cells is accompanied by an induction of the expression of the apoptotic form of the Bcl-x gene, the isoform Bcl-xS, and by a decrease of Bcl-2 expression, Bcl-xL remaining almost undetectable. The loss of mitochondrial membrane potential was associated with apoptosis. Z-VAD, a cell-permeable inhibitor of caspases, but not cycloheximide, precludes DNA laddering under serum deprivation. Moreover, Z-VAD rescues serum-deprived brown adipocytes from apoptosis, decreasing the percentage of hypodiploid cells, the percentage of apoptotic cells under Tunnel assay, and the external display of phosphatidylserine. More importantly, Z-VAD survival effects on immortalized brown adipocytes concur with a downregulation of Bcl-xS mRNA/protein and an upregulation of Bcl-2 protein content. Ultimately, Z-VAD prevents the loss of mitochondrial membrane potential.

Adipocytes↗

PubMed2002

Fibronectin promotes cell cycle entry in smooth muscle cells in primary culture.

Smooth muscle cell proliferation after arterial injury is regulated by growth factors and components of the extracellular matrix. We have previously demonstrated that fibronectin promotes a phenotypic modulation of freshly isolated rat smooth muscle cells from a contractile to a synthetic phenotype in primary culture and supports the ability of the cells to respond to growth factors. Here, we analyzed if fibronectin promotes cell cycle entry in freshly isolated rat aortic smooth muscle cells during primary culture. Cell cycle analysis showed that cells seeded on fibronectin remained in the G(0)/G(1) phase of the cell cycle during the first 6 days of culture. During this period, there was an increased expression of cyclin D1 and p27(KIP1) in the absence of exogenous growth factors. Addition of serum was followed by enhanced cyclin D1 expression, decreased p27(KIP1) levels, hyperphosphorylation of Rb protein, induction of cyclin A and cyclin D3 expression, and cell cycle progression into S phase. The results indicate that fibronectin initiates cell cycle entry in freshly isolated smooth muscle cells by promoting the induction of cyclin D1 and thereby facilitates further cell cycle progression together with growth factors.

Animals↗

PubMed1997

The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21(WAF1/CIP1/SDI1) in a p53-independent manner.

Recently we have shown that in fibroblasts (NIH 3T3 and Rat-1 cells) inhibition of protein geranylgeranylation leads to a G0/G1 arrest, whereas inhibition of protein farnesylation does not affect cell cycle distribution. Here we demonstrate that in human tumor cells the geranylgeranyltransferase-I (GGTase-I) inhibitor GGTI-298 blocked cells in G0/G1, whereas the farnesyltransferase (FTase) inhibitor FTI-277 showed a differential effect depending on the cell line. FTI-277 accumulated Calu-1 and A-549 lung carcinoma and Colo 357 pancreatic carcinoma cells in G2/M, T-24 bladder carcinoma, and HT-1080 fibrosarcoma cells in G0/G1, but had no effect on cell cycle distribution of pancreatic (Panc-1), breast (SKBr 3 and MDAMB-231), and head and neck (A-253) carcinoma cells. Furthermore, treatment of Calu-1, Panc-1, Colo 357, T-24, A-253, SKBr 3, and MDAMB-231 cells with GGTI-298, but not FTI-277, induced the protein expression levels of the cyclin-dependent kinase inhibitor p21WAF. HT-1080 and A-549 cells had a high basal level of p21WAF, and GGTI-298 did not further increase these levels. Furthermore, GGTI-298 also induces the accumulation of large amounts of p21WAF mRNA in Calu-1 cells, a cell line that lacks the tumor suppressor gene p53. There was little effect of GGTI-298 on the cellular levels of another cyclin- dependent kinase inhibitor p27KIP as well as cyclin E and cyclin D1. These results demonstrate that GGTase-I inhibitors arrest cells in G0/G1 and induce accumulation of p21WAF in a p53-independent manner and that FTase inhibitors can interfere with cell cycle events by a mechanism that involves neither p21WAF nor p27KIP. The results also point to the potential of GGTase-I inhibitors as agents capable of restoring growth arrest in cells lacking functional p53.

Alkyl and Aryl Transferases↗

PubMed2004

Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation.

The inhibition of cyclin-dependent kinase activity by p27 contributes to regulation of cell cycle progression. Serine 10 is the major phosphorylation site of p27, and its phosphorylation has been shown to affect the stability and nuclear export of p27 at the G0-G1 transition in transfected cultured cells. To investigate the physiological relevance of p27 phosphorylation on Ser10, we generated p27 "knock-in" mice that harbor an S10A mutation in this protein. Mice homozygous for the mutation (p27(S10A/S10A) mice) were normal in body size, but the abundance of p27 was decreased in many organs, including brain, thymus, spleen, and testis. The stability of p27 in G0 phase was markedly reduced in lymphocytes of p27(S10A/S10A) mice compared with that in wild-type cells, whereas p27 stability in S phase was similar in cells of the two genotypes. The degradation of p27 in cells of the mutant mice at G0 phase was prevented by a proteasome inhibitor. These data indicate that the physiological role of p27 phosphorylation on Ser10 is to stabilize the protein in G0 phase. Unexpectedly, the nuclear export of p27 at the G0-G1 transition occurred normally in p27(S10A/S10A) mouse embryonic fibroblasts, indicating that phosphorylation of Ser10 is dispensable for this process.

Active Transport, Cell Nucleus↗

PubMed1991

Stimulation of bumetanide-sensitive Na+/K+/Cl- cotransport by different mitogens in synchronized human skin fibroblasts is essential for cell proliferation.

In this study, we examined the role of the bumetanide-sensitive Na+/K+/Cl- cotransport in the mitogenic signal of human skin fibroblast proliferation. The Na+/K+/Cl- cotransport was dramatically stimulated by either fetal calf serum, or by recombinant growth factors, added to quiescent G0/G1 human skin fibroblasts. The following mitogens, FGF, PDGF, alpha-thrombin, insulin-like growth factor-1, transforming growth factor-alpha, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate, all stimulated the Na+/K+/Cl- cotransport. In addition, all the above mitogens induced DNA synthesis in the synchronized human fibroblasts. In order to explore the role of the Na+/K+/Cl- cotransport in the mitogenic signal, the effect of two specific inhibitors of the cotransport, furosemide and bumetanide, was tested on cell proliferation induced by the above recombinant growth factors. Bumetanide and furosemide inhibited synchronized cell proliferation as was measured by (a) cell exit from the G0/G1 phase measured by the use of flow cytometry, (b) cell entering the S-phase, determined by DNA synthesis, and (c) cell growth, measured by counting the cells. The inhibition by furosemide and bumetanide was reversible, removal of these compounds, completely released the cells from the block of DNA synthesis. In addition, the two drugs inhibited DNA synthesis only when added within the first 2-6 h of cell release. These results indicate that the effect of these drugs is specific, and is not due to an indirect toxic effect. This study clearly demonstrates that the growth factor-induced activation of the Na+/K+/Cl- cotransport plays a major role in the mitogenic signaling pathway of the human fibroblasts.

Bumetanide↗

PubMed2003

Commitment point during G0-->G1 that controls entry into the cell cycle.

Initiation of T-lymphocyte-mediated immune responses involves two cellular processes: entry into the cell cycle (G(0)-->G(1)) for clonal proliferation and coordinated changes in surface and secreted molecules that mediate effector functions. However, a point during G(0)-->G(1) beyond which T cells are committed to enter the cell cycle has not been defined. We define here a G(0)-->G(1) commitment point that occurs 3 to 5 h after CD3 and CD28 stimulation of human CD4 or CD8 T cells. Transition through this point requires cdk6/4-cyclin D, since inhibition with TAT-p16(INK4A) during the first 3 to 5 h prevents cell cycle entry and maintains both naive and memory T cells in G(0). Transition through the G(0)-->G(1) commitment point is also necessary for T cells to increase in size, i.e., to enter the cellular growth cycle. However, transition through this point is not required for the induction of effector functions. These can be initiated while cells are maintained in G(0) with TAT-p16(INK4A). We have termed this quiescent, activated state G(0(A)). Our data provide proof of the principle that entry of T cells into the cell cycle and cellular growth cycles are coupled at the G(0)-->G(1) commitment point but that these processes can be uncoupled from the early expression of molecules of effector functions.

Antibodies↗

PubMed2002

Enhanced sensitivity of G1 arrested human cancer cells suggests a novel therapeutic strategy using a combination of simvastatin and TRAIL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells over normal cells. To study the relationship between cell cycle progression and TRAIL-induced apoptosis, SW480 colon cancer and H460 lung cancer cell lines were examined for their sensitivity to TRAIL after arrest in different cell cycle phases. Cells were synchronized in G0/G1, S, and G2/M phase by serum starvation, aphidicolin, or nocodazole treatment, respectively. We found that arrest of cells in G0/G1 phase confers significantly higher susceptibility to TRAIL-induced apoptosis as compared to cells in late G1, S, or G2/M phase. To determine if cell cycle phase could be harnessed for therapeutic gain in the presence of TRAIL, we used the HMG-CoA reductase inhibitor, Simvastatin and lovastatin, to enrich a cancer cell population in G0/G1. Both simvastatin and lovastatin significantly augmented TRAIL-induced apoptosis in tumor cells, but not in normal keratinocytes. The results indicate that TRAIL, in combination with a HMG-CoA reductase inhibitor, may have therapeutic potential in the treatment of human cancer.

Antineoplastic Agents↗

PubMed2002

NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines.

Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time- and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX-2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS-398 in hepatocellular carcinoma cell lines.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Mice lacking Pin1 develop normally, but are defective in entering cell cycle from G(0) arrest.

The peptidyl prolil cis/trans isomerase Ess1/Pin1 is essential for mitosis progression in yeast cells and is hypothesized to perform the same role in mammalian cells. To investigate the function of Pin1 in mammalian cells, we created mice lacking Pin1. These mice underwent normal development. Although the embryonic Pin1-/- fibroblasts grew normally, they proved significantly deficient in their ability to restart proliferation in response to serum stimulation after G(0) arrest. These results suggest that Pin1 is required for cell cycle progression from G(0) arrest as well as mitosis progression in normal mammalian cells.

Amino Acid Sequence↗

PubMed1999

Hydrogen peroxide induces nuclear translocation of p53 and apoptosis in cells of oligodendroglia origin.

The observation that apoptosis is an inherent pathway in oligodendrocytes development coupled with the notion that wild-type p53 is expressed in these cells, prompted us to investigate the interrelationship between the two phenomena. Using a permanent oligodendroglia-like cell line (OLN 93), we examined the role of p53 protein in apoptosis following a DNA insult induced by a brief exposure to H2O2. A marked translocation of p53 from the cytosolic to the nuclear compartment was notable by 20 min, following a 5 min treatment with 1 mM H2O2 as identified by cell immunostaining. By 48 h following H2O2 addition, nearly 60% of the cells exhibited p53 in the nuclei. At this time, a large proportion of the cells underwent apoptosis as identified by DAPI nuclear staining. The genotoxic-induced p53 relocalization appeared to be cell cycle phase specific; thus OLN 93 cultures enriched for cells in the G0/G1 stage by serum starvation, and abundant in nuclear-associated p53, were more susceptible to H2O2-induced apoptosis than their untreated counterparts and than double thymidine block, G1/S enriched, cultures. Analysis of the expression of p53 downstream genes indicated that p21 and mdm2 were upregulated following p53 nuclear translocation. From the kinetics of protein accumulation, it appears that mdm2 enhancement accelerated the exit of p53 from the nucleus to the cytosol. Our results suggest that following stress, oligodendroglia-like cells are induced to undergo p53-dependent apoptosis, an event that coincides with p53 nuclear translocation and is cell-cycle related.

Animals↗

PubMed2002

Delayed liver regeneration in peroxisome proliferator-activated receptor-alpha-null mice.

Peroxisome proliferator chemicals, acting via the peroxisome proliferator-activated receptor-alpha (Pparalpha), are potent hepatic mitogens and carcinogens in mice and rats. To test whether Pparalpha is required for hepatic growth in response to other stimuli, we studied liver regeneration and hepatic gene expression following partial hepatectomy (PH) of wild-type and Pparalpha-null mice. Pparalpha-null mice had a 12- to 24-hour delay in liver regeneration associated with a delayed onset and lower peak magnitude of hepatocellular DNA synthesis. Furthermore, these mice had a 24-hour lag in the hepatic expression of the G(1)/S checkpoint regulator genes Ccnd1 and cMyc and increased expression of the IL-1beta cytokine gene. Hepatic expression of Ccnd1, cMyc, IL-1r1, and IL-6r was induced in wild-type mice, but not Pparalpha-null mice, after acute exposure to the potent Pparalpha agonist Wy-14,643, indicating a role for Pparalpha in regulating the expression of these genes. Expression of the fatty acid omega-hydroxylase gene Cyp4a14, a commonly used indicator gene for Pparalpha activation, was strongly induced in wild-type mice after hepatectomy, suggesting that altered hepatocyte lipid processing may also contribute to the impaired regeneration in mice lacking the Pparalpha gene. In conclusion, liver regeneration in Pparalpha-null mice is transiently impaired and is associated with altered expression of genes involved in cell cycle control, cytokine signaling, and fat metabolism.

Animals↗

PubMed2006

Activated Src abrogates the Myc requirement for the G0/G1 transition but not for the G1/S transition.

The transcription factor Myc plays a central role in the control of cellular proliferation. Myc expression is induced by growth factors in a pathway mediated by cellular Src (c-Src), but it is not clear whether Myc induction or activity is required for malignant transformation by activated Src. We introduced v-Src into a c-myc(-/-) derivative of Rat-1 fibroblasts and into 3T9 mouse fibroblasts harboring a conditionally excisable c-myc allele. Expression of activated viral Src in Myc-deficient cells led to loss of actin stress fibers and surface fibronectin, indicating that Myc is dispensable for v-Src-induced morphological transformation. However, v-Src failed to rescue the proliferative defect resulting from the loss of Myc. In Myc-deficient cells, despite its inability to overcome this proliferation block, v-Src was able to regulate the expression of certain Myc transcriptional targets and induce the expression of active cyclin D/Cdk4 and Cdk6 complexes; it also induced the phosphorylation of Rb, albeit at reduced levels. In contrast, however, in the absence of Myc, the level of Cdk2 kinase activity was drastically reduced. This reduction in Cdk2 activity was associated with a decrease in the expression of Cdk7, Cdc25A, and cyclin A. Coexpression of Cdk2 plus cyclin E and/or cyclin A rescued the G1/S block and allowed the cells to enter mitosis. These results indicate that in the absence of Myc, v-Src can activate early G1 cell cycle regulators but fails to activate regulators of the late G1/S transition.

Animals↗

PubMed2004

Molecular analysis of p21 promoter activity isolated from squamous carcinoma cell lines of the head and neck under the influence of 1,25(OH)2 vitamin D3 and its analogs.

OBJECTIVE: The biologically active 1,25(OH)2 vitamin D3 and its analogs have been shown to have antiproliferative and differentiating effects in a variety of malignant and non-malignant cells. For squamous carcinoma cell lines of the head and neck (SCCHN) we could show that this antiproliferative activity of 1,25(OH)2 vitamin D3 is due to induced expression of the cell-cycle inhibitory proteins p21 and p27, causing an arrest in the G0/G1 cell-cycle phase. MATERIAL AND METHODS: In this work we investigated the effects of three vitamin D3 analogs, EB1089, MC1288 and CB1093, on proliferation behavior and cell-cycle status in a laryngeal carcinoma cell line (JPPA) as well as in control human immortalized keratinocytes (HaCaT). To study the molecular mechanism the functional activity of the promoter region of p21, a potential target gene of vitamin D3 transcriptional regulation, was investigated. For this reason a 2.7-kb fragment of the p21 promoter was isolated by polymerase chain reaction from HaCaT, JPPA and SCC9 (tongue carcinoma) cells and directionally cloned into an enhanced green fluorescence protein (EGFP) reporter gene vector system. A construct was used to stably transfect HaCaT cells and to monitor the expression of the EGFP gene by confocal microscopy. RESULTS: Analysis of proliferation and cell-cycle status revealed decreased growth rates and G0/G1I cell-cycle arrest in cells treated with 1,25(OH)2 vitamin D3 and its analogs The EGFP reporter gene-transfected cells showed distinct fluorescence under the influence of 1,25(OH)2 vitamin D3 and its analogs compared to control cells. CONCLUSION: These results demonstrate that the cell-cycle inhibitor protein p21 is a direct target gene of biologically active 1,25(OH)2 vitamin D3, inducing G0/G1 cell-cycle arrest. The ability of vitamin D analogs to act via the same molecular mechanism as the natural hormone but with less hypercalcemic activity may have therapeutic implications for patients with SCCHN malignancy.

Antineoplastic Agents↗

PubMed2001

Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase.

We report that prosaposin treatment induced extracellular signal-regulated kinases (ERKs) and sphingosine kinase activity, increased DNA synthesis, and prevented cell apoptosis. Prosaposin treatment induced pheochromocytoma cells (PC12) to enter the S phase of the cell cycle; this effect was inhibited by the MEK inhibitor PD98059, indicating that prosaposin-induced ERK phosphorylation is required for stimulation of DNA synthesis. The prosaposin effect was also inhibited by pertussis toxin, indicating that the prosaposin receptor is a G-protein-coupled receptor. Prosaposin rescued PC12 cells from apoptosis induced by staurosporine or ceramide. Sphingosine kinase activity was increased by prosaposin treatment. We propose that this effect is a mechanism underlying the proliferative and anti-apoptotic functions of prosaposin. Prosaposin appears to be a key regulatory factor in the ceramide-S-1-P rheostat, which regulates cell fate.

Adrenal Gland Neoplasms↗

PubMed2005

Changing chromatin dynamics and nuclear organization during differentiation in Drosophila larval tissue.

Global changes in gene expression and exit from the cell cycle underlie differentiation. Therefore, understanding chromatin behavior in differentiating nuclei and late G1 is key to understanding this developmental event. A nuclear event that has been shown to specifically occur in late G1 is the association of two heterochromatic blocks in Drosophila. The brown(Dominant) (bw(D)) chromosome of Drosophila melanogaster contains a large block of heterochromatin near the end of 2R. This distal block associates with centric heterochromatin (2Rh), but not until at least 5 hours into G1. We used the bw(D) allele as a model for nuclear organization to determine whether its association with the heterochromatic compartment of the second chromosomes (2Rh) strictly requires differentiation or if this change is a stochastic event, its occurrence being proportional to time spent in G1/G0 phase of the cell cycle. Fluorescence in situ hybridization on eye imaginal discs showed increased association between the bw locus and 2Rh in differentiated cells. Interestingly, an increase in the number of nuclei showing bw(D)-2Rh association in the brains of developmentally delayed larvae that were compromised for differentiation was also observed. Live fluorescence imaging showed that the kinetics of chromatin movement remains unchanged in the developmentally arrested nuclei. These observations suggest that nuclear reorganization is not directly controlled by specific inductive signals during differentiation and that this nuclear reorganization can happen in a cell, regardless of differentiation state, that is arrested in the appropriate cell cycle stage. However, we did see changes that appear to be more directly correlated with differentiation. Dynamic imaging in eye imaginal discs showed that the movement of chromatin is more constrained in differentiated cells, implying that confinement of loci to a smaller nuclear space may help to maintain the changed organization and the transcription profile that accompanies differentiation.

Alleles↗