scholarly journals Elimination Of Aberrantly Specified Cell Clones Is Independent Of Interfacial Myosin II Accumulation

2021 ◽  
Author(s):  
Olga Klipa ◽  
Fisun Hamaratoglu
Keyword(s):  
Spatial Organization ◽  
Myosin Ii ◽  
Cell Types ◽  
Wild Type ◽  
Apical Constriction ◽  
Cell Clones ◽  
Distinct Cell ◽  
Tensile Forces ◽  
Muscle Myosin

Spatial organization of differently fated cells within an organ is essential and needs to be maintained during development. This is largely implemented via compartment boundaries that serve as barriers between distinct cell types. Biased accumulation of junctional non-muscle Myosin II along the interface between differently fated groups of cells contributes to boundary integrity and maintains its shape via increased tension. Here we test whether interfacial Myosin driven tension is responsible for the elimination of aberrantly specified cells that would otherwise compromise compartment organization. To this end, we genetically reduce Myosin II levels in three different patterns: in both wild-type and misspecified cells, only in misspecified cells and specifically at the interface between wild-type and aberrantly specified cells. We find that recognition and elimination of aberrantly specified cells do not rely on tensile forces driven by interfacial Myosin cables. Moreover, apical constriction of misspecified cells and their separation from wild type neighbors occurs even when Myosin level is greatly reduced. Thus, we conclude that the forces that drive elimination of aberrantly specified cells are largely independent of Myosin II.

scholarly journals Mechanical bistability enabled by ectodermal compression facilitates Drosophila mesoderm invagination

2021 ◽  
Author(s):  
Hanqing Guo ◽  
Michael Swan ◽  
Shicheng Huang ◽  
Bing He
Keyword(s):  
Myosin Ii ◽  
Cell Sheet ◽  
Apical Surface ◽  
Apical Constriction ◽  
Out Of Plane ◽  
A Cell ◽  
Plane Compression ◽  
Contractile Forces ◽  
Tissue Relaxation ◽  
Muscle Myosin

Apical constriction driven by non-muscle myosin II (″myosin″) provides a well-conserved mechanism to mediate epithelial folding. It remains unclear how contractile forces near the apical surface of a cell sheet drive out-of-plane bending of the sheet and whether myosin contractility is required throughout folding. By optogenetic-mediated acute inhibition of myosin, we find that during Drosophila mesoderm invagination, myosin contractility is critical to prevent tissue relaxation during the early, ″priming″ stage of folding but is dispensable for the actual folding step after the tissue passes through a stereotyped transitional configuration, suggesting that the mesoderm is mechanically bistable during gastrulation. Combining computer modeling and experimental measurements, we show that the observed mechanical bistability arises from an in-plane compression from the surrounding ectoderm, which promotes mesoderm invagination by facilitating a buckling transition. Our results indicate that Drosophila mesoderm invagination requires a joint action of local apical constriction and global in-plane compression to trigger epithelial buckling.

scholarly journals p11 modulates L-DOPA therapeutic effects and dyskinesia via distinct cell types in experimental Parkinsonism

2016 ◽  
Vol 113 (5) ◽  
pp. 1429-1434 ◽  
Author(s):  
Nicoletta Schintu ◽  
Xiaoqun Zhang ◽  
Alexandra Alvarsson ◽  
Roberta Marongiu ◽  
Michael G. Kaplitt ◽  
...  
Keyword(s):  
Side Effects ◽  
Glutamate Release ◽  
Adaptor Protein ◽  
Cell Types ◽  
Dopamine Neurons ◽  
Therapeutic Effects ◽  
Wild Type ◽  
Distinct Cell ◽  
Experimental Mouse ◽  
Nigrostriatal Dopamine Neurons

The reduced movement repertoire of Parkinson’s disease (PD) is mainly due to degeneration of nigrostriatal dopamine neurons. Restoration of dopamine transmission by levodopa (L-DOPA) relieves motor symptoms of PD but often causes disabling dyskinesias. Subchronic L-DOPA increases levels of adaptor protein p11 (S100A10) in dopaminoceptive neurons of the striatum. Using experimental mouse models of Parkinsonism, we report here that global p11 knockout (KO) mice develop fewer jaw tremors in response to tacrine. Following L-DOPA, global p11KO mice show reduced therapeutic responses on rotational motor sensitization, but also develop less dyskinetic side effects. Studies using conditional p11KO mice reveal that distinct cell populations mediate these therapeutic and side effects. Selective deletion of p11 in cholinergic acetyltransferase (ChAT) neurons reduces tacrine-induced tremor. Mice lacking p11 in dopamine D2R-containing neurons have a reduced response to L-DOPA on the therapeutic parameters, but develop dyskinetic side effects. In contrast, mice lacking p11 in dopamine D1R-containing neurons exhibit tremor and rotational responses toward L-DOPA, but develop less dyskinesia. Moreover, coadministration of rapamycin with L-DOPA counteracts L-DOPA–induced dyskinesias in wild-type mice, but not in mice lacking p11 in D1R-containing neurons. 6-OHDA lesioning causes an increase of evoked striatal glutamate release in wild type, but not in global p11KO mice, indicating that altered glutamate neurotransmission could contribute to the reduced L-DOPA responsivity. These data demonstrate that p11 located in ChAT or D2R-containing neurons is involved in regulating therapeutic actions in experimental PD, whereas p11 in D1R-containing neurons underlies the development of L-DOPA–induced dyskinesias.

scholarly journals Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions

2021 ◽  
Author(s):  
Laura Glorieux ◽  
Aleksandra Sapala ◽  
David Willnow ◽  
Manon Moulis ◽  
Shlomit Edri ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Current Knowledge ◽  
Image Data ◽  
Light Sheet ◽  
Cell Types ◽  
Pancreatic Tissue ◽  
Embryonic Cell ◽  
Cell Interactions ◽  
Distinct Cell

AbstractGenerating comprehensive image maps, while preserving spatial 3D context, is essential to quantitatively assess and locate specific cellular features and cell-cell interactions during organ development. Despite the recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is still largely based on 2D histological sections. Here, we present a light-sheet fluorescence microscopy approach to image the pancreas in 3D and map tissue interactions at key development time points in the mouse embryo. We used transgenic mouse models and antibodies to visualize the three main cellular components within the developing pancreas, including epithelial, mesenchymal and endothelial cell populations. We demonstrated the utility of the approach by providing volumetric data, 3D distribution of distinct progenitor populations and quantification of relative cellular abundance within the tissue. Lastly, our image data were combined in an open source online repository (referred to as Pancreas Embryonic Cell Atlas). This image dataset will serve the scientific community by enabling further investigation on pancreas organogenesis but also for devising strategies for the in vitro generation of transplantable pancreatic tissue for regenerative therapies.

scholarly journals LMO7-dependent apical constriction requires the binding of the Myosin heavy chain

2021 ◽  
Author(s):  
Miho Matsuda ◽  
Chih-Wen Chu ◽  
Sergei S Sokol
Keyword(s):  
Heavy Chain ◽  
Myosin Light Chain ◽  
Myosin Ii ◽  
Tube Formation ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Apical Domain ◽  
Underlying Mechanisms ◽  
Muscle Myosin

The reduction of the apical domain, or apical constriction, is a process that occurs in a single cell or is coordinated in a group of cells in the epithelium. Coordinated apical constriction is particularly important when the epithelium is undergoing dynamic morphogenetic events such as furrow or tube formation. However, the underlying mechanisms remain incompletely understood. Here we show that Lim only protein 7 (Lmo7) is a novel activator of apical constriction in the Xenopus superficial ectoderm, which coordinates actomyosin contractility in a group of cells during epithelial morphogenesis. Like other apical constriction regulators, Lmo7 requires the activation of the Rho-Rock-Myosin II pathway to induce apical constriction. However, instead of increasing the phosphorylation of myosin light chain (MLC), Lmo7 binds muscle myosin II heavy chain A (NMIIA) and increases its association with actomyosin bundles at adherens junctions (AJs). Lmo7 overexpression modulates the subcellular distribution of Wtip, a tension marker at AJs, suggesting that Lmo7 generates mechanical forces at AJs. We propose that Lmo7 increases actomyosin contractility at AJs by promoting the formation of actomyosin bundles.

scholarly journals Cortical contraction drives the 3D patterning of epithelial cell surfaces

2019 ◽  
Author(s):  
Aaron P. van Loon ◽  
Ivan S. Erofeev ◽  
Ivan V. Maryshev ◽  
Andrew B. Goryachev ◽  
Alvaro Sagasti
Keyword(s):  
Surface Tension ◽  
Myosin Ii ◽  
Biomechanical Model ◽  
Cell Surfaces ◽  
Apical Constriction ◽  
Skin Cells ◽  
In Vivo Experiments ◽  
Surface Topographies ◽  
Muscle Myosin

ABSTRACTCellular protrusions create complex cell surface topographies, but biomechanical mechanisms regulating their formation and arrangement are largely unknown. To study how protrusions form, we focused on the morphogenesis of microridges, elongated actin-based structures projecting from the apical surfaces of zebrafish skin cells that are arranged in labyrinthine patterns. Microridges form by accreting simple finger-like precursors. Live imaging demonstrated that microridge morphogenesis is linked to apical constriction. A non-muscle myosin II (NMII) reporter revealed pulsatile contractions of the actomyosin cortex; inhibiting NMII demonstrated that contractions are required for apical constriction and microridge formation. A biomechanical model suggested that contraction reduces surface tension to permit the fusion of precursors into microridges. Indeed, reducing surface tension with hyperosmolar media promoted microridge formation. In anisotropically stretched cells, microridges formed by precursor fusion along the stretch axis, which computational modeling explained as a consequence of stretch-induced cortical flow. Collectively, our results demonstrate how contraction within the 2D plane of the cortex patterns 3D cell surfaces.SUMMARYMicroridges, elongated 3D protrusions arranged in maze-like patterns on zebrafish skin cells, form by the accretion of simple precursor projections. Modeling and in vivo experiments showed that cortical contractions promote the coalescence of precursors into microridges by reducing membrane tension.

Pituitary ontogeny of the Snell dwarf mouse reveals Pit-1-independent and Pit-1-dependent origins of the thyrotrope

Development ◽  
1994 ◽  
Vol 120 (3) ◽  
pp. 515-522 ◽  
Author(s):  
S.C. Lin ◽  
S. Li ◽  
D.W. Drolet ◽  
M.G. Rosenfeld
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Cell Phenotype ◽  
Specific Cell ◽  
Mutant Form ◽  
Wild Type ◽  
Pou Domain ◽  
Distinct Cell ◽  
Snell Dwarf ◽  
Dwarf Mice

The anterior pituitary provides a model to study the molecular mechanisms responsible for emergence of distinct cell types within an organ. Dwarf mice (Snell) that express a mutant form of the tissue-specific POU-domain transcription factor Pit-1 fail to generate three cell types, including the thyrotrope (S. Li, E. B. Crenshaw, E. J. Rawson, D. S. Simmons, L. Swanson and M. G. Rosenfeld (1990), Nature 347, 528–533). Analyses of wild-type and Pit-1-defective mice, presented here, have revealed that thyrotropes unexpectedly arise from two independent cell populations. The first population is Pit-1-independent and appears on e12 in the rostral tip of the developing gland, but phenotypically disappears by the day of birth. The second is Pit-1-dependent and arises subsequently in the caudomedial portion of the developing gland (e15.5), following the initial expression of Pit-1 in this region. The failure of caudomedial thyrotrope cells to appear in the Snell dwarf, and the observation that Pit-1 can bind to and transactivate the TSH beta promoter, apparently enhanced by its phosphorylation, suggests that Pit-1 is directly required for the appearance of this distinct population that serves as the precursors of the mature thyrotrope cell type. These data suggest that different molecular mechanisms, based on the actions of distinct transcription factors, can serve to independently generate a specific cell phenotype during mammalian organogenesis.

scholarly journals XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment

2021 ◽  
Vol 7 (17) ◽  
pp. eabg4755
Author(s):  
Youjin Lee ◽  
Derek Bogdanoff ◽  
Yutong Wang ◽  
George C. Hartoularos ◽  
Jonathan M. Woo ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Spatial Organization ◽  
Cell Types ◽  
Mouse Tumor ◽  
Spatially Resolved ◽  
Distinct Cell ◽  
Single Cell Rna Sequencing ◽  
A Cell ◽  
Anatomical Space

Single-cell RNA sequencing (scRNA-seq) of tissues has revealed remarkable heterogeneity of cell types and states but does not provide information on the spatial organization of cells. To better understand how individual cells function within an anatomical space, we developed XYZeq, a workflow that encodes spatial metadata into scRNA-seq libraries. We used XYZeq to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. Analyses of these data revealed the spatial distribution of distinct cell types and a cell migration-associated transcriptomic program in tumor-associated mesenchymal stem cells (MSCs). Furthermore, we identify localized expression of tumor suppressor genes by MSCs that vary with proximity to the tumor core. We demonstrate that XYZeq can be used to map the transcriptome and spatial localization of individual cells in situ to reveal how cell composition and cell states can be affected by location within complex pathological tissue.

scholarly journals Liquid-crystal organization of liver tissue

2018 ◽  
Author(s):  
Hernán Morales-Navarrete ◽  
Hidenori Nonaka ◽  
André Scholich ◽  
Fabián Segovia-Miranda ◽  
Walter de Back ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Self Assembly ◽  
Liver Tissue ◽  
Spatial Organization ◽  
Structural Model ◽  
Cell Types ◽  
Soft Condensed Matter ◽  
Distinct Cell ◽  
Tissue Geometry ◽  
Organizing Principles

AbstractFunctional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells as generally assumed, since silencing Integrin-ß1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

scholarly journals Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies

2020 ◽  
Author(s):  
Laura E. Mickelsen ◽  
William F. Flynn ◽  
Kristen Springer ◽  
Lydia Wilson ◽  
Eric J. Beltrami ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Organization ◽  
Single Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Posterior Hypothalamus ◽  
Neuronal Populations ◽  
Mammillary Bodies ◽  
Distinct Cell ◽  
And Behavior

ABSTRACTThe ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell types in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in a selection of neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit a surprising degree of segregation within neuroanatomical subdivisions of the MB, while genetically-defined MB cell types project topographically to the anterior thalamus. This single cell transcriptomic atlas of cell types in the VPH provides a detailed resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits in health and disease.

scholarly journals Genetic regulation and pattern formation: A study of the yellow locus in Drosophila melanogaster

1974 ◽  
Vol 24 (1) ◽  
pp. 19-26 ◽  
Author(s):  
William G. Nash ◽  
Rhoda J. Yarkin
Keyword(s):  
Drosophila Melanogaster ◽  
Pattern Formation ◽  
Genetic Regulation ◽  
Phenotypic Expression ◽  
Type A ◽  
Cell Types ◽  
Wild Type ◽  
Unique Pattern ◽  
Distinct Cell ◽  
Different Cell Types

SUMMARYMany of the yellow alleles found in Drosophila melanogaster result in a unique pattern of phenotypic expression. These patterns follow the morphologically distinct cell types of the cuticle, so that for one allele all the bristles of the head and thorax might be mutant, while most of the fly appears wild type. A comparison of many different y mutants demonstrates that the yellow phenotype is expressed independently in most if not all the different cell types which form the cuticle. Control of this expression appears to reside at the yellow locus itself.

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