Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (100)

Search Parameters:
Keywords = asymmetric cell division

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
8 pages, 2184 KB  
Brief Report
X-Ray Crystal Structure of the N-Terminal Domain of Staphylococcus Aureus Cell-Cycle Protein GpsB
by Nathan I. Nicely, Thomas. M. Bartlett and Richard W. Baker
Crystals 2025, 15(10), 867; https://doi.org/10.3390/cryst15100867 - 30 Sep 2025
Viewed by 149
Abstract
GpsB is a conserved cell-cycle regulator in the Firmicute clade of Gram-positive bacteria that coordinates multiple aspects of envelope biogenesis. Recent studies demonstrate interactions between GpsB and the key division cytoskeleton FtsZ, suggesting that GpsB links cell division to various aspects of cell [...] Read more.
GpsB is a conserved cell-cycle regulator in the Firmicute clade of Gram-positive bacteria that coordinates multiple aspects of envelope biogenesis. Recent studies demonstrate interactions between GpsB and the key division cytoskeleton FtsZ, suggesting that GpsB links cell division to various aspects of cell envelope biogenesis in Staphylococcus aureus and potentially other Firmicutes. We determined a 1.7 Å resolution crystal structure of the N-terminal domain of Staphylococcus aureus GpsB, revealing an asymmetric dimer with a bent conformation. This conformation is nearly identical to one of two conformations reported by Sacco et al., confirming the unique conformation of S. aureus GpsB compared to other Gram-positive bacteria. This structural agreement provides strong validation of the S. aureus GpsB fold and supports its proposed role in organizing the cell division machinery. Full article
(This article belongs to the Section Biomolecular Crystals)
20 pages, 5322 KB  
Article
Regulation of Tetraspanin CD63 in Chronic Myeloid Leukemia (CML): Single-Cell Analysis of Asymmetric Hematopoietic Stem Cell Division Genes
by Christophe Desterke, Annelise Bennaceur-Griscelli and Ali G. Turhan
Bioengineering 2025, 12(8), 830; https://doi.org/10.3390/bioengineering12080830 - 31 Jul 2025
Viewed by 675
Abstract
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity [...] Read more.
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article
(This article belongs to the Special Issue Micro- and Nano-Technologies for Cell Analysis)
Show Figures

Graphical abstract

23 pages, 2571 KB  
Communication
Duchenne Muscular Dystrophy Patient iPSCs—Derived Skeletal Muscle Organoids Exhibit a Developmental Delay in Myogenic Progenitor Maturation
by Urs Kindler, Lampros Mavrommatis, Franziska Käppler, Dalya Gebrehiwet Hiluf, Stefanie Heilmann-Heimbach, Katrin Marcus, Thomas Günther Pomorski, Matthias Vorgerd, Beate Brand-Saberi and Holm Zaehres
Cells 2025, 14(13), 1033; https://doi.org/10.3390/cells14131033 - 7 Jul 2025
Cited by 1 | Viewed by 1514
Abstract
Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle [...] Read more.
Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Stem Cell-Derived Organoids)
Show Figures

Figure 1

10 pages, 895 KB  
Opinion
Latest News from the “Guardian”: p53 Directly Activates Asymmetric Stem Cell Division Regulators
by Ana Carmena
Int. J. Mol. Sci. 2025, 26(7), 3171; https://doi.org/10.3390/ijms26073171 - 29 Mar 2025
Viewed by 947
Abstract
Since its discovery in 1979, the human tumor suppressor gene TP53—also known as the “guardian of the genome”—has been the subject of intense research. Mutated in most human cancers, TP53 has traditionally been considered a key fighter against stress factors by trans-activating [...] Read more.
Since its discovery in 1979, the human tumor suppressor gene TP53—also known as the “guardian of the genome”—has been the subject of intense research. Mutated in most human cancers, TP53 has traditionally been considered a key fighter against stress factors by trans-activating a network of target genes that promote cell cycle arrest, DNA repair, or apoptosis. Intriguingly, over the past years, novel non-canonical functions of p53 in unstressed cells have also emerged, including the mode of stem cell division regulation. However, the mechanisms by which p53 modulates these novel functions remain incompletely understood. In a recent work, we found that Drosophila p53 controls asymmetric stem cell division (ASCD) in neural stem cells by transcriptionally activating core ASCD regulators, such as the conserved cell-fate determinants Numb and Brat (NUMB and TRIM3/TRIM2/TRIM32 in humans, respectively). In this short communication, we comment on this new finding, the mild phenotypes associated with Drosophila p53 mutants in this context, as well as novel avenues for future research. Full article
Show Figures

Figure 1

14 pages, 6635 KB  
Article
Slope Calculation Analysis Based on Arbitrary Polygonal Hybrid Stress Elements Considering Gravity
by Chang Liu, Jingjie Tian, Changhao Hu, Fan Xia, Runjie Wang, Xuyang Wei and Ying Xu
Symmetry 2025, 17(2), 265; https://doi.org/10.3390/sym17020265 - 10 Feb 2025
Viewed by 710
Abstract
This article proposes an arbitrary polygonal hybrid stress element considering gravity. It derives an arbitrary polygonal hybrid stress element considering gravity alone for slope stability related engineering analysis. In the stability analysis of slopes, slope disasters caused by gravity erosion have recently become [...] Read more.
This article proposes an arbitrary polygonal hybrid stress element considering gravity. It derives an arbitrary polygonal hybrid stress element considering gravity alone for slope stability related engineering analysis. In the stability analysis of slopes, slope disasters caused by gravity erosion have recently become an urgent problem to be solved through engineering. The traditional finite element analysis of slope stability faces problems such as a large number of divided elements and slow calculation efficiency. By introducing high-order stress fields through stress hybridization elements, accurate results can be simulated using a small number of elements. When dividing the mesh, most of the cell shapes are asymmetric, and the shape of the cell can be any polygon, which can simulate the geometric shape of complex slopes well and more accurately calculate the stress distribution in different parts, thus accurately simulating the stability situation in engineering. By comparing with the corresponding commercial software MARC 2020, the effectiveness and efficiency of the element were verified. It has been proven that any polygonal hybrid stress element has the advantage of flexible mesh division, which can obtain high-order stress fields and stress concentration phenomena with fewer elements. Applying this element to practical problems of slopes in engineering has also achieved good calculation results. Full article
Show Figures

Figure 1

13 pages, 6504 KB  
Article
Germanium Metasurface for the Polarization-Sensitive Stokes Thermal Imaging at a MWIR 4-Micron Wavelength
by Hosna Sultana
Photonics 2025, 12(2), 137; https://doi.org/10.3390/photonics12020137 - 7 Feb 2025
Viewed by 1836
Abstract
The mid-wave infrared (MWIR) spectral range can provide a larger bandwidth for optical sensing and communication when the near-infrared band becomes congested. This range of thermal signatures can provide more information for digital imaging and object recognition, which can be unraveled from polarization-sensitive [...] Read more.
The mid-wave infrared (MWIR) spectral range can provide a larger bandwidth for optical sensing and communication when the near-infrared band becomes congested. This range of thermal signatures can provide more information for digital imaging and object recognition, which can be unraveled from polarization-sensitive detection by integrating the metasurface of the subwavelength-scale structured interface to control light–matter interactions. To enforce the metasurface-enabled simultaneous detection and parallel analysis of polarization states in a compact footprint for 4-micron wavelength, we designed a high-contrast germanium metasurface with an axially asymmetric triangular nanoantenna with a height 0.525 times the working wavelength. First, we optimized linear polarization separation of a 52-degree angle with about 50% transmission efficiency, holding the meta-element aspect ratio within the 3.5–1.67 range. The transmission modulation in terms of periodicity and lattice resonance for the phase-gradient high-contrast dielectric metasurface in correlation with the scattering cross-section for both 1D and 2D cases has been discussed for reducing the aspect ratio to overcome the nanofabrication challenge. Furthermore, by employing the geometric phase, we achieved 40% and 60% transmission contrasts for the linear and circular polarization states, respectively, and reconstructed the Stokes vectors and output polarization states. Without any spatial multiplexing, this single metasurface unit cell can perform well in the division of focal plane Stokes thermal imaging, with an almost 10-degree field of view, and it has an excellent refractive index and height tolerance for nanofabrication. Full article
Show Figures

Figure 1

24 pages, 5762 KB  
Article
Relative Distribution of DnaA and DNA in Escherichia coli Cells as a Factor of Their Phenotypic Variability
by Sharanya K. Namboodiri, Alexander Aranovich, Uzi Hadad, Levi A. Gheber, Mario Feingold and Itzhak Fishov
Int. J. Mol. Sci. 2025, 26(2), 464; https://doi.org/10.3390/ijms26020464 - 8 Jan 2025
Cited by 2 | Viewed by 1404
Abstract
Phenotypic variability in isogenic bacterial populations is a remarkable feature that helps them cope with external stresses, yet it is incompletely understood. This variability can stem from gene expression noise and/or the unequal partitioning of low-copy-number freely diffusing proteins during cell division. Some [...] Read more.
Phenotypic variability in isogenic bacterial populations is a remarkable feature that helps them cope with external stresses, yet it is incompletely understood. This variability can stem from gene expression noise and/or the unequal partitioning of low-copy-number freely diffusing proteins during cell division. Some high-copy-number components are transiently associated with almost immobile large assemblies (hyperstructures) and may be unequally distributed, contributing to bacterial phenotypic variability. We focus on the nucleoid hyperstructure containing numerous DNA-associated proteins, including the replication initiator DnaA. Previously, we found an increasing asynchrony in the nucleoid segregation dynamics in growing E. coli cell lineages and suggested that variable replication initiation timing may be the main cause of this phenomenon. Here, we support this hypothesis revealing that DnaA/DNA variability represents a key factor leading to the enhanced asynchrony in E. coli. We followed the intra- and intercellular distribution of fluorescently tagged DnaA and histone-like HU chromosomally encoded under their native promoters. The diffusion rate of DnaA is low, corresponding to a diffusion-binding mode of mobility, but still one order faster than that of HU. The intracellular distribution of DnaA concentration is homogeneous in contrast to the significant asymmetry in the distribution of HU to the cell halves, leading to the unequal DNA content of nucleoids and DnaA/DNA ratios in future daughter compartments. Accordingly, the intercellular variabilities in HU concentration (CV = 26%) and DnaA/DNA ratio (CV = 18%) are high. The variable DnaA/DNA may cause a variable replication initiation time (initiation noise). Asynchronous initiation at different replication origins may, in turn, be the mechanism leading to the observed asymmetric intracellular DNA distribution. Our findings indicate that the feature determining the variability of the initiation time in E. coli is the DnaA/DNA ratio, rather than each of them separately. We provide a likely mechanism for the ‘loss of segregation synchrony’ phenomenon. Full article
(This article belongs to the Special Issue Molecular Research on Bacteria)
Show Figures

Figure 1

14 pages, 6040 KB  
Article
LINE-1-Induced Retrotransposition Affects Early Preimplantation Embryo DNA Integrity and Pluripotency
by Prodromos Sakaloglou, Leandros Lazaros, Ioanna Bouba, Sofia Markoula, Athanasios Zikopoulos, Eirini Drakaki, Ismini Anagnostaki, Anastasios Potiris, Sofoklis Stavros, Angeliki Gerede, Ekaterini Domali, Peter Drakakis, Theodoros Tzavaras and Ioannis Georgiou
Int. J. Mol. Sci. 2024, 25(23), 12722; https://doi.org/10.3390/ijms252312722 - 27 Nov 2024
Cited by 1 | Viewed by 1467
Abstract
Retrotransposable elements are implicated in genome rearrangements and gene expression alterations that result in various human disorders. In the current study, we sought to investigate the potential effects of long interspersed elements-1 (LINE-1) overexpression on the integrity and methylation of DNA and on [...] Read more.
Retrotransposable elements are implicated in genome rearrangements and gene expression alterations that result in various human disorders. In the current study, we sought to investigate the potential effects of long interspersed elements-1 (LINE-1) overexpression on the integrity and methylation of DNA and on the expression of three major pluripotency factors (OCT4, SOX2, NANOG) during the preimplantation stages of human embryo development. Human MI oocytes were matured in vitro to MII and transfected through intracytoplasmic sperm injection (ICSI) either with an EGFP vector carrying a cloned active human LINE-1 retroelement or with the same EGFP vector without insert as control. The occurrence of retrotransposition events was screened by fluorescent microscopy. The in vitro preimplantation development as well as the methylation, pluripotency, and DNA double-strand breaks (DSBs) of the transfected embryos were examined. LINE-1 retrotransposons gave rise to new retrotransposition events in the transfected embryos. LINE-1 injected embryos were characterized by accelerated asymmetrical cell division, multiple cellular fragments, cleavage arrest, and degeneration. Early OCT4 expression remained unaltered, but cleavage arrest and a high fragmentation rate hindered the expression of SOX2/NANOG at the morula stage. Increased DNA DSBs were observed in cleavage-stage blastomeres, while no methylation changes were detected before the cleavage arrest. Our data provide evidence that LINE-1 retrotransposition in human preimplantation embryos may induce DNA DSBs, while at the same time, it appears to interfere with the expression patterns of pluripotency factors. The morphological, structural, and cleavage abnormalities of the transfected embryos show that aberrant retroelement expression may negatively affect human embryo development. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Show Figures

Figure 1

26 pages, 8311 KB  
Article
Notch-Dependent Expression of the Drosophila Hey Gene Is Supported by a Pair of Enhancers with Overlapping Activities
by Maria Monastirioti, Ioanna Koltsaki, Ioanna Pitsidianaki, Emilia Skafida, Nikolaos Batsiotos and Christos Delidakis
Genes 2024, 15(8), 1071; https://doi.org/10.3390/genes15081071 - 14 Aug 2024
Viewed by 1879
Abstract
Drosophila Hey is a basic helix–loop–helix–orange (bHLH-O) protein with an important role in the establishment of distinct identities of postmitotic cells. We have previously identified Hey as a transcriptional target and effector of Notch signalling during the asymmetric division of neuronal progenitors, generating [...] Read more.
Drosophila Hey is a basic helix–loop–helix–orange (bHLH-O) protein with an important role in the establishment of distinct identities of postmitotic cells. We have previously identified Hey as a transcriptional target and effector of Notch signalling during the asymmetric division of neuronal progenitors, generating neurons of two types, and we have shown that Notch-dependent expression of Hey also marks a subpopulation of the newborn enteroendocrine (EE) cells in the midgut primordium of the embryo. Here, we investigate the transcriptional regulation of Hey in neuronal and intestinal tissues. We isolated two genomic regions upstream of the promoter (HeyUP) and in the second intron (HeyIN2) of the Hey gene, based on the presence of binding motifs for Su(H), the transcription factor that mediates Notch activity. We found that both regions can direct the overlapping expression patterns of reporter transgenes recapitulating endogenous Hey expression. Moreover, we showed that while HeyIN2 represents a Notch-dependent enhancer, HeyUP confers both Notch-dependent and independent transcriptional regulation. We induced mutations that removed the Su(H) binding motifs in either region and then studied the enhancer functionality in the respective Hey mutant lines. Our results provide direct evidence that although both enhancers support Notch-dependent regulation of the Hey gene, their role is redundant, as a Hey loss-of-function lethal phenotype is observed only after deletion of all their Su(H) binding motifs by CRISPR/Cas9. Full article
Show Figures

Figure 1

18 pages, 4271 KB  
Review
Spatio-Temporal Regulation of Notch Activation in Asymmetrically Dividing Sensory Organ Precursor Cells in Drosophila melanogaster Epithelium
by Mathieu Pinot and Roland Le Borgne
Cells 2024, 13(13), 1133; https://doi.org/10.3390/cells13131133 - 30 Jun 2024
Cited by 1 | Viewed by 1801
Abstract
The Notch communication pathway, discovered in Drosophila over 100 years ago, regulates a wide range of intra-lineage decisions in metazoans. The division of the Drosophila mechanosensory organ precursor is the archetype of asymmetric cell division in which differential Notch activation takes place at [...] Read more.
The Notch communication pathway, discovered in Drosophila over 100 years ago, regulates a wide range of intra-lineage decisions in metazoans. The division of the Drosophila mechanosensory organ precursor is the archetype of asymmetric cell division in which differential Notch activation takes place at cytokinesis. Here, we review the molecular mechanisms by which epithelial cell polarity, cell cycle and intracellular trafficking participate in controlling the directionality, subcellular localization and temporality of mechanosensitive Notch receptor activation in cytokinesis. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
Show Figures

Figure 1

15 pages, 9853 KB  
Article
Adar Regulates Drosophila melanogaster Spermatogenesis via Modulation of BMP Signaling
by Qian Zhang, Xinxin Fan, Fang Fu, Yuedan Zhu, Guanzheng Luo and Haiyang Chen
Int. J. Mol. Sci. 2024, 25(11), 5643; https://doi.org/10.3390/ijms25115643 - 22 May 2024
Viewed by 2055
Abstract
The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet [...] Read more.
The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis. Full article
(This article belongs to the Section Molecular Biology)
Show Figures

Figure 1

29 pages, 2210 KB  
Review
The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective
by Sudhir Verma, Xiao Lin and Vivien J. Coulson-Thomas
Cells 2024, 13(9), 748; https://doi.org/10.3390/cells13090748 - 25 Apr 2024
Viewed by 2802
Abstract
Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population [...] Read more.
Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population of stem cells resides in the limbal region, named the limbal epithelial stem cells (LESCs). As LESCs proliferate, they generate TACs that move centripetally into the cornea and differentiate into corneal epithelial cells. Upon limbal injury, research suggests a population of progenitor-like cells that exists within the cornea can move centrifugally into the limbus, where they dedifferentiate into LESCs. Herein, we summarize recent advances made in understanding the mechanism that governs the differentiation of LESCs into TACs, and thereafter, into corneal epithelial cells. We also outline the evidence in support of the existence of progenitor-like cells in the cornea and whether TACs could represent a population of cells with progenitor-like capabilities within the cornea. Furthermore, to gain further insights into the dynamics of TACs in the cornea, we outline the most recent findings in other organ systems that support the hypothesis that TACs can dedifferentiate into SCs. Full article
(This article belongs to the Collection Stem Cells in Tissue Engineering and Regeneration)
Show Figures

Figure 1

11 pages, 1852 KB  
Article
Transcriptomic Profiling at the Maternal-to-Zygotic Transition in Leech, Helobdella austinensis
by Samuel Hsaio, Naim Saglam, David Morrow and Daniel H. Shain
Genes 2024, 15(3), 283; https://doi.org/10.3390/genes15030283 - 24 Feb 2024
Cited by 1 | Viewed by 2188
Abstract
The glossiphoniid leech, Helobdella austinensis, is an experimentally tractable member of the superphylum, Lophotrochozoa. Its large embryonic cells, stereotyped asymmetric cell divisions and ex vivo development capabilities makes it a favorable model for studying the molecular and cellular events of a representative [...] Read more.
The glossiphoniid leech, Helobdella austinensis, is an experimentally tractable member of the superphylum, Lophotrochozoa. Its large embryonic cells, stereotyped asymmetric cell divisions and ex vivo development capabilities makes it a favorable model for studying the molecular and cellular events of a representative spiralian. In this study, we focused on a narrow developmental time window of ~6–8 h, comprising stages just prior to and immediately following zygote deposition. Employing RNA-Seq methodology, we identified differentially expressed transcripts at this fundamental ontogenic boundary, known as the maternal-to-zygotic transition (MZT). Gene expression changes were characterized by the massive degradation of maternal RNAs (~45%) coupled with the rapid transcription of ~5000 zygotic genes (~20% of the genome) in the first mitotic cell cycle. The latter transcripts encoded a mixture of cell maintenance and regulatory proteins that predictably influence downstream developmental events. Full article
Show Figures

Figure 1

15 pages, 6442 KB  
Article
LLGL2 Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via ACTN1
by Qiu-Ying Gu, Yue-Xi Liu, Jin-Long Wang, Xiao-Lan Huang, Ruo-Nan Li and Hua Linghu
Cancers 2023, 15(24), 5880; https://doi.org/10.3390/cancers15245880 - 18 Dec 2023
Cited by 6 | Viewed by 2309
Abstract
Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in [...] Read more.
Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells. Full article
(This article belongs to the Section Cancer Metastasis)
Show Figures

Figure 1

21 pages, 5794 KB  
Article
Separable Roles for Neur and Ubiquitin in Delta Signalling in the Drosophila CNS Lineages
by Konstantina Kalodimou, Margarita Stapountzi, Nicole Vüllings, Ekaterina Seib, Thomas Klein and Christos Delidakis
Cells 2023, 12(24), 2833; https://doi.org/10.3390/cells12242833 - 14 Dec 2023
Cited by 1 | Viewed by 1720
Abstract
The execution of a Notch signal at the plasma membrane relies on the mechanical force exerted onto Notch by its ligand. It has been appreciated that the DSL ligands need to collaborate with a ubiquitin (Ub) ligase, either Neuralized or Mindbomb1, in order [...] Read more.
The execution of a Notch signal at the plasma membrane relies on the mechanical force exerted onto Notch by its ligand. It has been appreciated that the DSL ligands need to collaborate with a ubiquitin (Ub) ligase, either Neuralized or Mindbomb1, in order to exert this pulling force, but the role of ubiquitylation per se is uncertain. Regarding the Delta–Neur pair, it is documented that neither the Neur catalytic domain nor the Delta intracellular lysines (putative Ub acceptors) are needed for activity. Here, we present a dissection of the Delta activity using the Delta–Notch-dependent expression of Hey in newborn Drosophila neurons as a sensitive in vivo assay. We show that the Delta–Neur interaction per se, rather than ubiquitylation, is needed for activity, pointing to the existence of a Delta–Neur signaling complex. The Neur catalytic domain, although not strictly needed, greatly improves Delta–Neur complex functionality when the Delta lysines are mutated, suggesting that the ubiquitylation of some component of the complex, other than Delta, can enhance signaling. Since Hey expression is sensitive to the perturbation of endocytosis, we propose that the Delta–Neur complex triggers a force-generating endocytosis event that activates Notch in the adjacent cell. Full article
(This article belongs to the Special Issue Molecular Studies of Drosophila Signaling Pathways)
Show Figures

Figure 1

Back to TopTop