scholarly journals The Ran pathway uniquely regulates cytokinesis in cells with different fates in the early C. elegans embryo

2021 ◽  
Author(s):  
Imge Ozugergin ◽  
Karina Mastronardi ◽  
Chris Law ◽  
Alisa Piekny
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Contractile Ring ◽  
C Elegans ◽  
Multiple Parameters ◽  
Daughter Cells ◽  
The Core ◽  
Cortical Patterning ◽  
Different Cell Types ◽  
In Cells

ABSTRACTCytokinesis occurs at the end of mitosis and occurs due to the ingression of a contractile ring that cleaves the daughter cells. This process is tightly controlled to prevent cell fate changes or aneuploidy, and the core machinery is highly conserved among metazoans. Multiple mechanisms regulate cytokinesis, but their requirement in different cell types is not known. Here, we show that differently fated AB and P1 cells in the early C. elegans embryo have unique cytokinesis kinetics supported by distinct levels and cortical patterning of myosin. Through perturbation of polarity regulators and the generation of stable tetraploid strains, we demonstrate that these differences depend on both cell fate and size. Additionally, these parameters could influence the Ran pathway, which coordinates the contractile ring with chromatin position, and controls cytokinesis differently in AB and P1 cells. Our findings demonstrate the need to consider multiple parameters when modeling ring kinetics.

scholarly journals Diverse mechanisms regulate contractile ring assembly for cytokinesis in the two-cell C. elegans embryo

2022 ◽  
Author(s):  
Imge Ozugergin ◽  
Karina Mastronardi ◽  
Chris Law ◽  
Alisa Piekny
Keyword(s):  
Cell Types ◽  
Somatic Tissue ◽  
Ring Closure ◽  
Contractile Ring ◽  
C Elegans ◽  
Daughter Cells ◽  
The Core ◽  
Ring Assembly ◽  
Different Cell Types ◽  
Ring Position

Cytokinesis occurs at the end of mitosis due to the ingression of a contractile ring that cleaves the daughter cells. The core machinery regulating this crucial process is conserved among metazoans. Multiple pathways control ring assembly, but their contribution in different cell types is not known. We found that in the C. elegans embryo, AB and P1 cells fated to be somatic tissue and germline, respectively, have different cytokinesis kinetics supported by distinct myosin levels and organization. Through perturbation of RhoA or polarity regulators and the generation of tetraploid strains, we found that ring assembly is controlled by multiple fate-dependent factors that include myosin-levels, and mechanisms that respond to cell size. Active Ran coordinates ring position with the segregating chromatids in HeLa cells by forming an inverse gradient with importins that control the cortical recruitment of anillin. We found that the Ran pathway regulates anillin in AB cells, but functions differently in P1 cells. We propose that ring assembly delays in P1 cells caused by low myosin and Ran signaling coordinate the timing of ring closure with their somatic neighbours.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

scholarly journals Core-shell bioprinting as a strategy to apply differentiation factors in a spatially defined manner inside osteochondral tissue substitutes

2021 ◽  
Author(s):  
David Kilian ◽  
Silvia Cometta ◽  
Anne Bernhardt ◽  
Rania Taymour ◽  
Jonas Golde ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Close Contact ◽  
Release Kinetics ◽  
Cell Types ◽  
Core Shell ◽  
The Core ◽  
Differentiation Factors ◽  
Local Supply ◽  
Osteochondral Tissue ◽  
Different Cell Types

Abstract One of the key challenges in osteochondral tissue engineering is to define specified zones with varying material properties, cell types and biochemical factors supporting locally adjusted differentiation into the osteogenic and chondrogenic lineage, respectively. Herein, extrusion-based core-shell bioprinting is introduced as a potent tool allowing a spatially defined delivery of cell types and differentiation factors TGF-β3 and BMP-2 in separated compartments of hydrogel strands, and, therefore, a local supply of matching factors for chondrocytes and osteoblasts. Ink development was based on blends of alginate and methylcellulose, in combination with varying concentrations of the nanoclay Laponite whose high affinity binding capacity for various molecules was exploited. Release kinetics of model molecules was successfully tuned by Laponite addition. Core-shell bioprinting was proven to generate well-oriented compartments within one strand as monitored by optical coherence tomography in a non-invasive manner. Chondrocytes and osteoblasts were applied each in the shell while the respective differentiation factors (TGF-β3, BMP-2) were provided by a Laponite-supported core serving as central factor depot within the strand, allowing directed differentiation of cells in close contact to the core. Experiments with bi-zonal constructs, comprising an osteogenic and a chondrogenic zone, revealed that the local delivery of the factors from the core reduces effects of these factors on the cells in the other scaffold zone. These observations prove the general suitability of the suggested system for co-differentiation of different cell types within a zonal construct.

Directing osteogenic differentiation of BMSCs by cell-secreted decellularized extracellular matrixes from different cell types

2018 ◽  
Vol 6 (45) ◽  
pp. 7471-7485 ◽  
Author(s):  
Chen-Yuan Gao ◽  
Zhao-Hui Huang ◽  
Wei Jing ◽  
Peng-Fei Wei ◽  
Le Jin ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Tissue Regeneration ◽  
Cell Types ◽  
Different Cell Types

Cell-secreted decellularized extracellular matrixes (D-ECM) are promising for conferring bioactivity and directing cell fate to facilitate tissue regeneration.

scholarly journals Optogenetic model reveals cell shape regulation through FAK and Fascin

2021 ◽  
Author(s):  
Jean A. Castillo-Badillo ◽  
N. Gautam
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cell Shape ◽  
Spherical Shape ◽  
Cell Types ◽  
Experimental Models ◽  
Molecular Processes ◽  
Different Cell Types ◽  
Shape Changes ◽  
In Cells

Cell shape regulation is important but the mechanisms that govern shape are not fully understood, in part due to limited experimental models where cell shape changes and underlying molecular processes can be rapidly and non-invasively monitored in real time. Here, we use an optogenetic tool to activate RhoA in the middle of mononucleated macrophages to induce contraction, resulting in a side with the nucleus that retains its shape and a non-nucleated side which was unable to maintain its shape and collapsed. In cells overexpressing focal adhesion kinase (FAK), the non-nucleated side exhibited a wide flat morphology and was similar in adhesion area to the nucleated side. In cells overexpressing fascin, an actin bundling protein, the non-nucleated side assumed a spherical shape and was similar in height to the nucleated side. This effect of fascin was also observed in fibroblasts even without inducing furrow formation. Based on these results, we conclude that FAK and fascin work together to maintain cell shape by regulating adhesion area and height, respectively, in different cell types.

scholarly journals Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Radek Jankele ◽  
Rob Jelier ◽  
Pierre Gönczy
Keyword(s):  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cell Lineage ◽  
External Compression ◽  
Cycle Progression ◽  
Spindle Positioning ◽  
C Elegans ◽  
Daughter Cells ◽  
Asymmetric Divisions ◽  
Cell Positioning

Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division ofCaenorhabditis elegansembryos, which yields a large AB cell and a small P1cell. We equalized AB and P1sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1descendants, as well as defects in cell positioning, division orientation, and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development ofC. elegans.

scholarly journals Exploratory analysis of transposable elements expression in the C. elegans early embryo

2019 ◽  
Vol 20 (S9) ◽  
Author(s):  
Federico Ansaloni ◽  
Margherita Scarpato ◽  
Elia Di Schiavi ◽  
Stefano Gustincich ◽  
Remo Sanges
Keyword(s):  
Nervous System ◽  
Transposable Elements ◽  
Embryo Development ◽  
Cell Types ◽  
Early Embryo ◽  
Bioinformatics Pipeline ◽  
Early Embryo Development ◽  
C Elegans ◽  
Differentiated Cells ◽  
Different Cell Types

Abstract Background Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. Results We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. Conclusions TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development.

scholarly journals Combinatorial Control of Exon Recognition

2007 ◽  
Vol 283 (3) ◽  
pp. 1211-1215 ◽  
Author(s):  
Klemens J. Hertel
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Cell Types ◽  
Splice Sites ◽  
Splice Site Selection ◽  
Multiple Parameters ◽  
Splicing Regulators ◽  
Eukaryotic Genes ◽  
Different Cell Types ◽  
Mature Mrnas

Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome, which catalyzes the removal of noncoding intronic sequences to assemble exons into mature mRNAs prior to export and translation. Given the complexity of higher eukaryotic genes and the relatively low level of splice site conservation, the precision of the splicing machinery in recognizing and pairing splice sites is impressive. Introns ranging in size from <100 up to 100,000 bases are removed efficiently. At the same time, a large number of alternative splicing events are observed between different cell types, during development, or during other biological processes. This extensive alternative splicing implies a significant flexibility of the spliceosome to identify and process exons within a given pre-mRNA. To reach this flexibility, splice site selection in higher eukaryotes has evolved to depend on multiple parameters such as splice site strength, the presence or absence of splicing regulators, RNA secondary structures, the exon/intron architecture, and the process of pre-mRNA synthesis itself. The relative contributions of each of these parameters control how efficiently splice sites are recognized and flanking introns are removed.

Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 837-844 ◽  
Author(s):  
L.A. Moore ◽  
H.T. Broihier ◽  
M. Van Doren ◽  
R. Lehmann
Keyword(s):  
Cell Fate ◽  
Fat Body ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Body Development ◽  
Developmental Relationship ◽  
Close Juxtaposition ◽  
Fate Decision ◽  
Different Cell Types ◽  
Lateral Mesoderm

During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10–12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4–9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.

scholarly journals Spatiotemporal cellular movement and fate decisions during first pharyngeal arch morphogenesis

2020 ◽  
Vol 6 (51) ◽  
pp. eabb0119
Author(s):  
Yuan Yuan ◽  
Yong-hwee Eddie Loh ◽  
Xia Han ◽  
Jifan Feng ◽  
Thach-Vu Ho ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Compartment Model ◽  
Cell Types ◽  
Pharyngeal Arch ◽  
Cell Fate Decision ◽  
Fate Decision ◽  
Fate Restriction ◽  
Different Cell Types ◽  
Cellular Movement

Cranial neural crest (CNC) cells contribute to different cell types during embryonic development. It is unknown whether postmigratory CNC cells undergo dynamic cellular movement and how the process of cell fate decision occurs within the first pharyngeal arch (FPA). Our investigations demonstrate notable heterogeneity within the CNC cells, refine the patterning domains, and identify progenitor cells within the FPA. These progenitor cells undergo fate bifurcation that separates them into common progenitors and mesenchymal cells, which are characterized by Cdk1 and Spry2/Notch2 expression, respectively. The common progenitors undergo further bifurcations to restrict them into osteogenic/odontogenic and chondrogenic/fibroblast lineages. Disruption of a patterning domain leads to specific mandible and tooth defects, validating the binary cell fate restriction process. Different from the compartment model of mandibular morphogenesis, our data redefine heterogeneous cellular domains within the FPA, reveal dynamic cellular movement in time, and describe a sequential series of binary cell fate decision-making process.

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