scholarly journals Establishment of signaling interactions with cellular resolution for every cell cycle of embryogenesis

2018 ◽  
Author(s):  
Long Chen ◽  
Vincy Wing Sze Ho ◽  
Ming-Kin Wong ◽  
Xiaotai Huang ◽  
Lu-yan Chan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Notch Signaling ◽  
Cell Lineage ◽  
Cellular Interaction ◽  
Cell Contact ◽  
Contact Map ◽  
C Elegans ◽  
Cellular Resolution ◽  
Signaling Interactions ◽  
Lineage Analysis

AbstractIntercellular signaling interaction plays a key role in breaking fate symmetry during animal development. Identification of the signaling interaction at cellular resolution is technically challenging, especially in a developing embryo. Here we develop a platform that allows automated inference and validation of signaling interaction for every cell cycle of C. elegans embryogenesis. This is achieved by generation of a systems-level cell contact map that consists of 1,114 highly confident intercellular contacts by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of Notch signaling pathway with cellular resolution using automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during C. elegans embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions over cell division in breaking fate symmetry. We finally develop a website that allows online access to the cell-cell contact map for mapping of other signaling interaction in the community. The platform can be adapted to establish cellular interaction from any other signaling pathways.

scholarly journals Visualizing the metazoan proliferation-terminal differentiation decision in vivo

2019 ◽  
Author(s):  
Rebecca C. Adikes ◽  
Abraham Q. Kohrman ◽  
Michael A. Q. Martinez ◽  
Nicholas J. Palmisano ◽  
Jayson J. Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Cell Lineage ◽  
Terminal Differentiation ◽  
Cyclin Dependent Kinase ◽  
C Elegans ◽  
Differentiated Cells ◽  
Imaging Tool ◽  
Wide Range

SummaryCell proliferation and terminal differentiation are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these cell cycle-associated events live in C. elegans and zebrafish. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from terminally differentiated cells in G0, revealing a commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. We also derive a predictive model of future proliferation behavior in C. elegans and zebrafish based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell cycle control in a wide-range of developmental contexts.

scholarly journals Cell‐cycle regulation of NOTCH signaling during C. elegans vulval development

2012 ◽  
Vol 8 (1) ◽  
pp. 618 ◽  
Author(s):  
Stefanie Nusser‐Stein ◽  
Antje Beyer ◽  
Ivo Rimann ◽  
Magdalene Adamczyk ◽  
Nir Piterman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Notch Signaling ◽  
Cell Cycle Regulation ◽  
Vulval Development ◽  
C Elegans ◽  
Cycle Regulation

scholarly journals Establishment of Signaling Interactions with Cellular Resolution for Every Cell Cycle of Embryogenesis

Genetics ◽  
2018 ◽  
Vol 209 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Long Chen ◽  
Vincy Wing Sze Ho ◽  
Ming-Kin Wong ◽  
Xiaotai Huang ◽  
Lu-yan Chan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cellular Resolution ◽  
Signaling Interactions

scholarly journals Establishment of a morphological atlas of the Caenorhabditis elegans embryo using deep-learning-based 4D segmentation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jianfeng Cao ◽  
Guoye Guan ◽  
Vincy Wing Sze Ho ◽  
Ming-Kin Wong ◽  
Lu-Yan Chan ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Morphology ◽  
Cell Biology ◽  
Cell Lineage ◽  
Time Lapse ◽  
Lineage Tracing ◽  
Cell Contact ◽  
C Elegans ◽  
Division Cell

AbstractThe invariant development and transparent body of the nematode Caenorhabditis elegans enables complete delineation of cell lineages throughout development. Despite extensive studies of cell division, cell migration and cell fate differentiation, cell morphology during development has not yet been systematically characterized in any metazoan, including C. elegans. This knowledge gap substantially hampers many studies in both developmental and cell biology. Here we report an automatic pipeline, CShaper, which combines automated segmentation of fluorescently labeled membranes with automated cell lineage tracing. We apply this pipeline to quantify morphological parameters of densely packed cells in 17 developing C. elegans embryos. Consequently, we generate a time-lapse 3D atlas of cell morphology for the C. elegans embryo from the 4- to 350-cell stages, including cell shape, volume, surface area, migration, nucleus position and cell-cell contact with resolved cell identities. We anticipate that CShaper and the morphological atlas will stimulate and enhance further studies in the fields of developmental biology, cell biology and biomechanics.

scholarly journals Deterministic Nature of Cellular Position Noise During C. elegans Embryogenesis

2018 ◽  
Author(s):  
Xiaoyu Li ◽  
Zhiguang Zhao ◽  
Weina Xu ◽  
Rong Fan ◽  
Long Xiao ◽  
...  
Keyword(s):  
Molecular Level ◽  
Phenotypic Variability ◽  
Cell Lineage ◽  
Cellular Level ◽  
Cell Contact ◽  
Biological Noise ◽  
C Elegans ◽  
Depth Analysis ◽  
System Properties ◽  
Noise Buffering

ABSTRACTIndividuals with identical genotypes exhibit great phenotypic variability known as biological noise, which has broad implications. While molecular-level noise has been extensively studied, in-depth analysis of cellular-level noise is challenging. Here, we present a systems-level quantitative and functional analysis of noise in cellular position during embryogenesis, an important phenotype indicating differentiation and morphogenesis. We show that cellular position noise is deterministic, stringently regulated by intrinsic and extrinsic mechanisms. The noise level is determined by cell lineage identity and is coupled to developmental properties including embryonic localization, cell contact, and left-right symmetry. Cells follow a concordant low-high-low pattern of noise dynamics, and fate specification triggers a global down-regulation of noise that provide a noise-buffering strategy. Noise is stringently regulated throughout embryogenesis, especially during cell division and cell adhesion and gap junctions function to restrict noise. Collectively, our study reveals system properties and regulatory mechanisms of cellular noise control during development.

Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator inC. elegans

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2155-2165
Author(s):  
Ivana Kostić ◽  
Richard Roy
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Intestinal Cells ◽  
Specific Cell ◽  
Cell Cycle Regulators ◽  
Loss Of Function ◽  
C Elegans ◽  
Cell Divisions

The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.

scholarly journals NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development

2019 ◽  
Author(s):  
Jie Li ◽  
Julie Gordon ◽  
Edward L. Y. Chen ◽  
Luying Wu ◽  
Juan Carlos Zúñiga-Pflücker ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cell ◽  
Notch Signaling ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Thymic Epithelial Cell ◽  
Self Tolerance ◽  
Medullary Thymic Epithelial Cell ◽  
History Of ◽  
Lineage Analysis

AbstractThe cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that Notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced Notch signaling in all TEC resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a Notch signal, consistent with Notch signaling occurring in mTEC progenitors. Interestingly, this lineage analysis also showed that cTECs are divided between Notch lineage-positive and lineage-negative populations, identifying a previously unknown complexity in the cTEC lineage.

scholarly journals Visualizing the metazoan proliferation-quiescence decision in vivo

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rebecca C Adikes ◽  
Abraham Q Kohrman ◽  
Michael A Q Martinez ◽  
Nicholas J Palmisano ◽  
Jayson J Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Cell Cycle Control ◽  
Cell Lineage ◽  
Live Cell ◽  
C Elegans ◽  
Imaging Tool ◽  
Wide Range

Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in C. elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell cycle control in a wide-range of developmental contexts.

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