scholarly journals Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2435-2446 ◽  
Author(s):  
Shin-ichi Ohnuma ◽  
Susannah Hopper ◽  
Kevin C. Wang ◽  
Anna Philpott ◽  
William A. Harris
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Cell Cycle Exit ◽  
Cyclin E1 ◽  
Distinct Cell ◽  
Cyclin Kinase Inhibitor ◽  
Notch Activation

The laminar arrays of distinct cell types in the vertebrate retina are built by a histogenic process in which cell fate is correlated with birth order. To explore this co-ordination mechanistically, we altered the relative timing of cell cycle exit in the developing Xenopus retina and asked whether this affected the activity of neural determinants. We found that Xath5, a bHLH proneural gene that promotes retinal ganglion cell (RGC) fate, (Kanekar, S., Perron, M., Dorsky, R., Harris, W. A., Jan, L. Y., Jan, Y. N. and Vetter, M. L. (1997) Neuron19, 981-994), does not cause these cells to be born prematurely. To drive cells out of the cell cycle early, therefore, we misexpressed the cyclin kinase inhibitor, p27Xic1. We found that early cell cycle exit potentiates the ability of Xath5 to promote RGC fate. Conversely, the cell cycle activator, cyclin E1, which inhibits cell cycle exit, biases Xath5-expressing cells toward later neuronal fates. We found that Notch activation in this system caused cells to exit the cell cycle prematuely, and when it is misexpressed with Xath5, it also potentiates the induction of RGCs. The potentiation is counteracted by co-expression of cyclin E1. These results suggest a model of histogenesis in which the activity of factors that promote early cell cycle exit enhances the activity of factors that promote early cellular fates.

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 Shaping of Drosophila Neural Cell Lineages Through Coordination of Cell Proliferation and Cell Fate by the BTB-ZF Transcription Factor Tramtrack-69

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 773-788
Author(s):  
Françoise Simon ◽  
Anne Ramat ◽  
Sophie Louvet-Vallée ◽  
Jérôme Lacoste ◽  
Angélique Burg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Cell Fate ◽  
Zinc Finger ◽  
Molecular Mechanisms ◽  
Neural Cell ◽  
Cell Cycle Exit ◽  
Cell Lineages ◽  
Accessory Cells

Cell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Using genetic approaches and correlative microscopy, we show that Tramtrack-69 (Ttk69, a Broad-complex, Tramtrack and Bric-à-brac - Zinc Finger (BTB-ZF) transcription factor ortholog of the human promyelocytic leukemia zinc finger factor) plays an essential role in controlling this balance. In the Drosophila bristle cell lineage, which produces the external sensory organs composed by a neuron and accessory cells, we show that ttk69 loss-of-function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell cycle exit of newborn terminal cells by downregulating CycE, the principal cyclin involved in S-phase entry, and (2) regulates cell-fate acquisition and terminal differentiation, by downregulating the expression of hamlet and upregulating that of Suppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell cycle exit and cell-fate commitment.

scholarly journals Regulatory network characterization in development: challenges and opportunities

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1477
Author(s):  
Guangdun Peng ◽  
Jing-Dong J. Han
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Mammalian Development ◽  
Distinct Cell ◽  
Challenges And Opportunities ◽  
Cell Processes ◽  
Early Mammalian Development

Embryonic development and stem cell differentiation, during which coordinated cell fate specification takes place in a spatial and temporal context, serve as a paradigm for studying the orderly assembly of gene regulatory networks (GRNs) and the fundamental mechanism of GRNs in driving lineage determination. However, knowledge of reliable GRN annotation for dynamic development regulation, particularly for unveiling the complex temporal and spatial architecture of tissue stem cells, remains inadequate. With the advent of single-cell RNA sequencing technology, elucidating GRNs in development and stem cell processes poses both new challenges and unprecedented opportunities. This review takes a snapshot of some of this work and its implication in the regulative nature of early mammalian development and specification of the distinct cell types during embryogenesis.

p21WAF1 Control of Epithelial Cell Cycle and Cell Fate

2002 ◽  
Vol 13 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Wendy C. Weinberg ◽  
Mitchell F. Denning
Keyword(s):  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Kinase Inhibitor ◽  
Growth Arrest ◽  
Nuclear Antigen ◽  
Central Position ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor

As a broad-acting cyclin-dependent kinase inhibitor, p21WAF1 occupies a central position in the cell cycle regulation of self-renewing tissues such as oral mucosa and skin. In addition to regulating normal cell cycle progression decisions, p21WAF1 integrates genotoxic insults into growth arrest and apoptotic signaling pathways that ultimately determine cell fate. As a result of its complex interactions with cell cycle machinery and response to mutagenic agents, p21WAF1 also has stage-specific roles in epithelial carcinogenesis. Finally, a view is emerging of p21WAF1 as not merely a cyclin-dependent kinase inhibitor, but also as a direct participant in regulating genes involved in growth arrest, senescence, and aging, thus providing an additional layer of control over matters of the cell cycle. This review discusses these various roles played by p21WAF1 in cell cycle control, and attempts to relate these to epithelial cell biology, with special emphasis on keratinocytes. (Abbreviations used include the following: Brdu, 5-Bromo-2-deoxyuridine; cdk, cyclin-dependent kinase; EGF, epidermal growth factor; KIP, kinase inhibitor protein; PCNA, proliferating cell nuclear antigen; and TPA, 12-O-tetradecanoylphorbol-13-acetate.)

scholarly journals Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function.

1996 ◽  
Vol 16 (9) ◽  
pp. 4952-4960 ◽  
Author(s):  
R L Ludwig ◽  
S Bates ◽  
K H Vousden
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cycle Arrest ◽  
P53 Tumor Suppressor Protein

The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.

Patterning of the angiosperm female gametophyte through the prism of theoretical paradigms

2014 ◽  
Vol 42 (2) ◽  
pp. 332-339 ◽  
Author(s):  
Dmytro S. Lituiev ◽  
Ueli Grossniklaus
Keyword(s):  
Cell Fate ◽  
Female Gametophyte ◽  
Positional Information ◽  
Cell Types ◽  
Theoretical Frameworks ◽  
Cell Specification ◽  
Distinct Cell ◽  
Dynamical Nature ◽  
Theoretical Paradigms ◽  
Lines Of Evidence

The FG (female gametophyte) of flowering plants (angiosperms) is a simple highly polar structure composed of only a few cell types. The FG develops from a single cell through mitotic divisions to generate, depending on the species, four to 16 nuclei in a syncytium. These nuclei are then partitioned into three or four distinct cell types. The mechanisms underlying the specification of the nuclei in the FG has been a focus of research over the last decade. Nevertheless, we are far from understanding the patterning mechanisms that govern cell specification. Although some results were previously interpreted in terms of static positional information, several lines of evidence now show that local interactions are important. In the present article, we revisit the available data on developmental mutants and cell fate markers in the light of theoretical frameworks for biological patterning. We argue that a further dissection of the mechanisms may be impeded by the combinatorial and dynamical nature of developmental cues. However, accounting for these properties of developing systems is necessary to disentangle the diversity of the phenotypic manifestations of the underlying molecular interactions.

scholarly journals Laminin β2 Chain Regulates Cell Cycle Dynamics in the Developing Retina

2022 ◽  
Vol 9 ◽  
Author(s):  
Dmitri Serjanov ◽  
Galina Bachay ◽  
Dale D. Hunter ◽  
William J. Brunken
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Critical Role ◽  
Laminin Receptor ◽  
Cell Cycle Exit ◽  
Cell Fate Decisions ◽  
M Phase ◽  
Cell Cycle Dynamics ◽  
Laminin Β2

Vertebrate retinal development follows a highly stereotyped pattern, in which the retinal progenitor cells (RPCs) give rise to all retinal types in a conserved temporal sequence. Ensuring the proper control over RPC cell cycle exit and re-entry is, therefore, crucially important for the generation of properly functioning retina. In this study, we demonstrate that laminins, indispensible ECM components, at the retinal surface, regulate the mechanisms determining whether RPCs generate proliferative or post-mitotic progeny. In vivo deletion of laminin β2 in mice resulted in disturbing the RPC cell cycle dynamics, and premature cell cycle exit. Specifically, the RPC S-phase is shortened, with increased numbers of cells present in its late stages. This is followed by an accelerated G2-phase, leading to faster M-phase entry. Finally, the M-phase is extended, with RPCs dwelling longer in prophase. Addition of exogenous β2-containing laminins to laminin β2-deficient retinal explants restored the appropriate RPC cell cycle dynamics, as well as S and M-phase progression, leading to proper cell cycle re-entry. Moreover, we show that disruption of dystroglycan, a laminin receptor, phenocopies the laminin β2 deletion cell cycle phenotype. Together, our findings suggest that dystroglycan-mediated ECM signaling plays a critical role in regulating the RPC cell cycle dynamics, and the ensuing cell fate decisions.

scholarly journals Deceleration of cell cycle underpins a switch from proliferative- to terminal division in plant stomatal lineage

2021 ◽  
Author(s):  
Soon-Ki Han ◽  
Jiyuan Yang ◽  
Machiko Arakawa ◽  
Rie Iwasaki ◽  
Tomoaki Sakamoto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Control Plant ◽  
Time Lapse ◽  
Cell Types ◽  
Symmetric Division ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Asymmetric Divisions ◽  
Stomatal Lineage

Differentiation of specialized cell types from self-renewing progenitors requires precise cell cycle control. Plant stomata are generated through asymmetric divisions of a stem-cell-like precursor meristemoid followed by the single symmetric division that creates an adjustable pore surrounded by paired guard cells. The stomatal-lineage-specific transcription factor MUTE terminates the asymmetric divisions and triggers differentiation. However, the role of cell cycle machinery in this transition remains unknown. Through time-lapse imaging, we discover that the symmetric division is slower than the asymmetric division. We identify a plant-specific cyclin-dependent kinase inhibitor, SIAMESE-RELATED4 (SMR4), as a molecular brake that decelerates cell cycle during this transition. SMR4 is directly induced by MUTE and transiently accumulates in differentiating meristemoids. SMR4 physically and functionally associates with CYCD3;1 and extends G1-phase of asymmetric divisions. By contrast, SMR4 fails to interact with CYCD5;1, a MUTE-induced G1 cyclin, and permits the symmetric division. Our work unravels a molecular framework of the proliferation-to-differentiation switch within the stomatal lineage and suggests that a timely proliferative cell cycle is critical for the stomatal fate specification.

scholarly journals Control of multiciliogenesis by miR-34/449 in the male reproductive tract through enforcing cell cycle exit

2021 ◽  
Author(s):  
Yu-Jie Wu ◽  
Yue Liu ◽  
Yan-Qin Hu ◽  
Li Wang ◽  
Fu-Rong Bai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Reproductive Tract ◽  
Surface Defects ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Apical Surface ◽  
Cell Cycle Exit ◽  
Double Knockout ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cilia Formation

Multiciliated cells (MCCs) are terminally differentiated, post-mitotic cells that possess hundreds of motile cilia on their apical surface. Defects in cilia formation are associated with ciliopathies that affect many organs. In the present study, we tested the role and mechanism of the miR-34/449 family in the regulation of multiciliogenesis in efferent ductules (EDs) using a miR-34b/c−/-; miR-449−/- double knockout (dKO) mouse model. MiR-34b/c and miR-449 depletion led to a reduced number of MCCs and abnormal cilia structure in the EDs starting from postnatal day 14. However, abnormal MCC differentiation in the dKO EDs could be observed as early as postnatal day 7. RNA-seq analyses revealed that the aberrant development of MCCs in the EDs of dKO mice was associated with upregulation of genes involved in cell cycle control. Using a cyclin dependent kinase inhibitor to force cell cycle exit promoted MCC differentiation, and partially rescued the defective multiciliogenesis in the EDs of dKO mice. Taken together, our results suggested that miR-34b/c and miR-449 play an essential role in multiciliogenesis in EDs by regulating cell cycle exit.

scholarly journals Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Zhang ◽  
Yueli Cui ◽  
Xinyi Ma ◽  
Jun Yong ◽  
Liying Yan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Human Pituitary ◽  
Pituitary Development ◽  
Physiological Processes ◽  
Distinct Cell ◽  
Transcriptional Landscape

Abstract The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.

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