scholarly journals Antagonistic roles of Polycomb repression and Notch signaling in the maintenance of somatic cell fate in C. elegans.

2016 ◽  
Author(s):  
Ringo Pueschel ◽  
Francesca Coraggio ◽  
Alisha Marti ◽  
Peter Meister
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Epigenetic Mark ◽  
Cell Plasticity ◽  
Cell Therapies ◽  
Polycomb Repressive Complex 2 ◽  
C Elegans ◽  
H3k27 Methylation ◽  
Histone H3k27

AbstractReprogramming of somatic cells in intact nematodes allows characterization of cell plasticity determinants, which knowledge is crucial for regenerative cell therapies. By inducing muscle or endoderm transdifferentiation by the ectopic expression of selector transcription factors, we show that cell fate is remarkably robust in fully differentiated larvae. This stability depends on the presence of the Polycomb-associated histone H3K27 methylation, but not H3K9 methylation: in the absence of this epigenetic mark, many cells can be transdifferentiated which correlates with definitive developmental arrest. A candidate RNAi screen unexpectedly uncovered that knock-down of somatic NotchLIN-12 signaling rescues this larval arrest. Similarly in a wild-type context, genetically increasing NotchLIN-12 signaling renders a fraction of the animals sensitive to induced transdifferentiation. This reveals an antagonistic role of the Polycomb repressive complex 2 stabilizing cell fate and Notch signaling enhancing cell plasticity.

scholarly journals Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Stefanie Seelk ◽  
Irene Adrian-Kalchhauser ◽  
Balázs Hargitai ◽  
Martina Hajduskova ◽  
Silvia Gutnik ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Germline Stem Cells ◽  
Polycomb Repressive Complex 2 ◽  
C Elegans ◽  
Functional Studies

Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling.

scholarly journals Polycomb Repressive Complex 2-mediated histone modification H3K27me3 is associated with embryogenic potential in Norway spruce

2020 ◽  
Vol 71 (20) ◽  
pp. 6366-6378 ◽  
Author(s):  
Miyuki Nakamura ◽  
Rita A Batista ◽  
Claudia Köhler ◽  
Lars Hennig
Keyword(s):  
Histone Modification ◽  
Cell Fate ◽  
Norway Spruce ◽  
Plant Species ◽  
Epigenetic Mark ◽  
Polycomb Repressive Complex ◽  
Embryogenic Potential ◽  
Polycomb Repressive Complex 2 ◽  
Embryonic Callus

Abstract Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT&RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.

Notch signaling is required for arterial-venous differentiation during embryonic vascular development

Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3675-3683 ◽  
Author(s):  
Nathan D. Lawson ◽  
Nico Scheer ◽  
Van N. Pham ◽  
Cheol-Hee Kim ◽  
Ajay B. Chitnis ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Blood Vessels ◽  
Cell Fate ◽  
Venous Blood ◽  
Vascular Development ◽  
Ectopic Expression ◽  
Specific Expression ◽  
Ectopic Activation ◽  
On Line ◽  
Embryonic Vascular Development

Recent evidence indicates that acquisition of artery or vein identity during vascular development is governed, in part, by genetic mechanisms. The artery-specific expression of a number of Notch signaling genes in mouse and zebrafish suggests that this pathway may play a role in arterial-venous cell fate determination during vascular development. We show that loss of Notch signaling in zebrafish embryos leads to molecular defects in arterial-venous differentiation, including loss of artery-specific markers and ectopic expression of venous markers within the dorsal aorta. Conversely, we find that ectopic activation of Notch signaling leads to repression of venous cell fate. Finally, embryos lacking Notch function exhibit defects in blood vessel formation similar to those associated with improper arterial-venous specification. Our results suggest that Notch signaling is required for the proper development of arterial and venous blood vessels, and that a major role of Notch signaling in blood vessels is to repress venous differentiation within developing arteries.Movies available on-line

scholarly journals Histone H3K27 methylation–mediated repression of Hairy regulates insect developmental transition by modulating ecdysone biosynthesis

2021 ◽  
Vol 118 (35) ◽  
pp. e2101442118
Author(s):  
Yan Yang ◽  
Tujing Zhao ◽  
Zheng Li ◽  
Wenliang Qian ◽  
Jian Peng ◽  
...  
Keyword(s):  
Larval Instar ◽  
Prothoracic Gland ◽  
Insect Development ◽  
Down Regulation ◽  
Developmental Defects ◽  
Polycomb Repressive Complex 2 ◽  
H3k27 Methylation ◽  
Developmental Transition ◽  
Histone H3k27 ◽  
Inhibitor Treatment

Insect development is cooperatively orchestrated by the steroid hormone ecdysone and juvenile hormone (JH). The polycomb repressive complex 2 (PRC2)–mediated histone H3K27 trimethylation (H3K27me3) epigenetically silences gene transcription and is essential for a range of biological processes, but the functions of H3K27 methylation in insect hormone action are poorly understood. Here, we demonstrate that H3K27 methylation–mediated repression of Hairy transcription in the larval prothoracic gland (PG) is required for ecdysone biosynthesis in Bombyx and Drosophila. H3K27me3 levels in the PG are dynamically increased during the last larval instar. H3K27me3 reduction induced by the down-regulation of PRC2 activity via inhibitor treatment in Bombyx or PG-specific knockdown of the PRC2 component Su(z)12 in Drosophila diminishes ecdysone biosynthesis and disturbs the larval–pupal transition. Mechanistically, H3K27 methylation targets the JH signal transducer Hairy to repress its transcription in the PG; PG-specific knockdown or overexpression of the Hairy gene disrupts ecdysone biosynthesis and developmental transition; and developmental defects caused by PG-specific Su(z)12 knockdown can be partially rescued by Hairy down-regulation. The application of JH mimic to the PG decreases both H3K27me3 levels and Su(z)12 expression. Altogether, our study reveals that PRC2-mediated H3K27 methylation at Hairy in the PG during the larval period is required for ecdysone biosynthesis and the larval–pupal transition and provides insights into epigenetic regulation of the crosstalk between JH and ecdysone during insect development.

scholarly journals DIV-1/PolA2 Promotes GLP-1/Notch-Mediated Cellular Events in Caenorhabditis elegans

2016 ◽  
Author(s):  
Dong Suk Yoon ◽  
Dong Seok Cha ◽  
Myon-Hee Lee
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
Critical Role ◽  
Germline Stem Cell ◽  
Notch Activity ◽  
C Elegans ◽  
Cellular Events ◽  
Somatic Tissues ◽  
Germline Proliferation

ABSTRACTNotch signaling is a highly conserved cell signaling system in most multicellular organisms and plays a critical role in animal development. In various tumor cells, Notch signaling is elevated and has been considered as an important target in cancer treatments. In C. elegans, GLP-1 (one of two C. elegans Notch receptors) activity is required for cell fate specification in germline and somatic tissues. In this study, we have identified div-1 gene as a positive regulator for GLP-1/Notch-mediated cellular events. C. elegans div-1 encodes the B subunit of the DNA polymerase alpha-primase complex and is highly expressed in proliferative germ cells. Functional analyses demonstrated that i) DIV-1 is required for the robust proliferation typical of the germline, ii) loss of DIV-1 enhances and suppresses specific phenotypes that are associated with reduced and elevated GLP-1/Notch activity in germline and somatic tissues, and iii) DIV-1 works together with FBF/PUF proteins, downstream regulators of GLP-1/Notch signaling, to promote germline stem cell (GSC) maintenance and germline proliferation. To maintain GSCs and proliferative cell fate, GLP-1/Notch activity must remain above a threshold for proliferation/differentiation decision. Our results propose that DIV-1 may control the level of threshold for GLP-1/Notch-mediated germline proliferation. PolA2, a mammalian homolog of the C. elegans DIV-1, has been emerged as a therapeutic target for non-small cell lung cancer (NSCLC). Notably, Notch signaling is altered in approximately one third of NSCLCs. Therefore, the discovery of the DIV-1 effect on GLP-1/Notch-mediated cellular events has implications for our understanding of vertebrate PolA2 protein and its influence on stem cell maintenance and tumorigenesis.

scholarly journals Polycomb and Notch signaling regulate cell proliferation potential duringCaenorhabditis eleganslife cycle

2018 ◽  
Vol 2 (1) ◽  
pp. e201800170 ◽  
Author(s):  
Francesca Coraggio ◽  
Ringo Püschel ◽  
Alisha Marti ◽  
Peter Meister
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Cell Fate ◽  
Essential Feature ◽  
Wild Type ◽  
H3k27 Methylation ◽  
Histone 3 ◽  
Proliferation And Differentiation ◽  
Multicellular Organisms ◽  
Proliferation Potential

Stable cell fate is an essential feature for multicellular organisms in which individual cells achieve specialized functions.Caenorhabditis elegansis a great model to analyze the determinants of cell fate stability because of its invariant lineage. We present a tractable cell fate challenge system that uses the induction of fate-specifying transcription factors. We show that wild-type differentiated animals are highly resistant to fate challenge. Removal of heterochromatin marks showed marked differences: the absence of histone 3 lysine 9 methylation (H3K9) has no effect on fate stability, whereas Polycomb homologmes-2mutants lacking H3K27 methylation terminally arrest larval development upon fate challenge. Unexpectedly, the arrest correlated with widespread cell proliferation rather than transdifferentiation. Using a candidate RNAi larval arrest-rescue screen, we show that the LIN-12Notchpathway is essential for hyperplasia induction. Moreover, Notch signaling appears downstream of food-sensing pathways, as dauers and first larval stage diapause animals are resistant to fate challenge. Our results demonstrate an equilibrium between proliferation and differentiation regulated by Polycomb and Notch signaling in the soma during the nematode life cycle.

scholarly journals Normal Patterns of Histone H3K27 Methylation Require the Histone Variant H2A.Z in Neurospora crassa

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Abigail J. Courtney ◽  
Masayuki Kamei ◽  
Aileen R. Ferraro ◽  
Kexin Gai ◽  
Qun He ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Embryonic Stem ◽  
Histone Variant ◽  
Genetic Studies ◽  
Polycomb Repressive Complex 2 ◽  
H3k27 Methylation ◽  
Experimental Systems ◽  
Polycomb Repression ◽  
Histone H3k27 ◽  
A Subunit

Neurospora crassa contains a minimal Polycomb repression system, which provides rich opportunities to explore Polycomb-mediated repression across eukaryotes and enables genetic studies that can be difficult in plant and animal systems. Polycomb Repressive Complex 2 is a multi-subunit complex that deposits mono-, di-, and trimethyl groups on lysine 27 of histone H3, and trimethyl H3K27 is a molecular marker of transcriptionally repressed facultative heterochromatin. In mouse embryonic stem cells and multiple plant species, H2A.Z has been found to be colocalized with H3K27 methylation. H2A.Z is required for normal H3K27 methylation in these experimental systems, though the regulatory mechanisms are not well understood. We report here that Neurospora crassa mutants lacking H2A.Z or SWR-1, the ATP-dependent histone variant exchanger, exhibit a striking reduction in levels of H3K27 methylation. RNA-sequencing revealed downregulation of eed, encoding a subunit of PRC2, in an hH2Az mutant compared to wild type, and overexpression of EED in a ΔhH2Az;Δeed background restored most H3K27 methylation. Reduced eed expression leads to region-specific losses of H3K27 methylation, suggesting that differential dependence on EED concentration is critical for normal H3K27 methylation at certain regions in the genome.

scholarly journals Canonical Notch Signaling Is Dispensable for Early Cell Fate Specifications in Mammals

2005 ◽  
Vol 25 (21) ◽  
pp. 9503-9508 ◽  
Author(s):  
Shaolin Shi ◽  
Mark Stahl ◽  
Linchao Lu ◽  
Pamela Stanley
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Sea Urchins ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Mammalian Development ◽  
Germ Layers ◽  
C Elegans ◽  
Conditional Deletion

ABSTRACT The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoderm, or ectoderm germ layers. Transcripts of Notch signaling pathway genes are present during mouse blastogenesis, suggesting that the canonical Notch signaling pathway may also function in early mammalian development. To test this directly, we used conditional deletion in oocytes carrying a ZP3Cre recombinase transgene to generate mouse embryos lacking both maternal and zygotic protein O-fucosyltransferase 1, a cell-autonomous and essential component of canonical Notch receptor signaling. Homozygous mutant embryos derived from eggs lacking Pofut1 gene transcripts developed indistinguishably from the wild type until approximately embryonic day 8.0, a postgastrulation stage after the formation of the three germ layers. Thus, in contrast to the case with C. elegans and sea urchins, canonical Notch signaling is not required in mammals for earliest cell fate specifications or for formation of the three germ layers. The use of canonical Notch signaling for early cell fate specifications by lower organisms may represent co-option of a regulatory pathway originally used later in development by all metazoa.

Barbu: an E(spl) m4/m(alpha)-related gene that antagonizes Notch signaling and is required for the establishment of ommatidial polarity

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1115-1130 ◽  
Author(s):  
S. Zaffran ◽  
M. Frasch
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Sequence Similarity ◽  
Ectopic Expression ◽  
Notch Pathway ◽  
Imaginal Discs ◽  
Notch Receptor ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Signaling Activity

The Notch signaling pathway is required, in concert with cell-type-specific transcriptional regulators and other signaling processes, for multiple cell fate decisions during mesodermal and ectodermal tissue development. In many instances, Notch signaling occurs initially in a bidirectional manner and then becomes unidirectional upon amplification of small inherent differences in signaling activity between neighboring cells. In addition to ligands and extracellular modulators of the Notch receptor, several intracellular proteins have been identified that can positively or negatively influence the activity of the Notch pathway during these dynamic processes. Here, we describe a new gene, Barbu, whose product can antagonize Notch signaling activity during Drosophila development. Barbu encodes a small and largely cytoplasmic protein with sequence similarity to the proteins encoded by the transcription units m4 and m(alpha) of the E(spl) complex. Ectopic expression studies with Barbu provide evidence that Barbu can antagonize Notch during lateral inhibition processes in the embryonic mesoderm, sensory organ specification in imaginal discs and cell type specification in developing ommatidia. Barbu loss-of-function mutations cause lethality and disrupt the establishment of planar polarity and photoreceptor specification in eye imaginal discs, which may also be a consequence of altered Notch signaling activities. Furthermore, in the embryonic neuroectoderm, Barbu expression is inducible by activated Notch. Taken together, we propose that Barbu functions in a negative feed-back loop, which may be important for the accurate adjustment of Notch signaling activity and the extinction of Notch activity between successive rounds of signaling events.

scholarly journals LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Pengpeng Li ◽  
Kevin M Collins ◽  
Michael R Koelle ◽  
Kang Shen
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Notch Signaling ◽  
Cell Fate ◽  
Dendritic Spine ◽  
Target Selection ◽  
Ectopic Expression ◽  
Cell Types ◽  
Synaptic Connectivity ◽  
Target Cells

The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells.

Sign in / Sign up

Export Citation Format

Share Document