scholarly journals BMP4 patterns Smad activity and generates stereotyped cell fate organisation in spinal organoids

2019 ◽  
Author(s):  
Nathalie Duval ◽  
Célia Vaslin ◽  
Tiago Barata ◽  
Stéphane Nédélec ◽  
Vanessa Ribes
Keyword(s):  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Neural Tube ◽  
Spatial Organization ◽  
Time Windows ◽  
Spatial Dynamics ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Dorsal Neural Tube ◽  
Bmp Signalling

AbstractBone Morphogenetic Proteins (BMP) are secreted regulators of cell fate in several developing tissues. In the embryonic spinal cord, they control the emergence of the neural crest, roof plate and distinct subsets of dorsal interneurons. Although a gradient of BMP activity has been proposed to determine cell type identity in vivo, whether this is sufficient for pattern formation in vitro is unclear. Here, we demonstrate that exposure to BMP4 initiates distinct spatial dynamics of BMP signalling within the self-emerging epithelia of both mouse and human pluripotent stem cells derived spinal organoids. The pattern of BMP signalling results in the stereotyped spatial arrangement of dorsal neural tube cell types and concentration, timing and duration of BMP4 exposure modulate these patterns. Moreover, differences in the duration of competence time-windows between mouse and human account for the species specific tempo of neural differentiation. Together the study describes efficient methods to generate patterned subsets of dorsal interneurons in spinal organoids and supports the conclusion that graded BMP activity orchestrates the spatial organization of the dorsal neural tube cellular diversity in mouse and human.

Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice

2001 ◽  
Vol 114 (24) ◽  
pp. 4429-4434
Author(s):  
Silvia Garagna ◽  
Maurizio Zuccotti ◽  
Alan Thornhill ◽  
Raul Fernandez-Donoso ◽  
Soledad Berrios ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Spatial Organization ◽  
Nuclear Architecture ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Condensed State ◽  
Germ Cell Differentiation ◽  
Y Chromosomes ◽  
Dual Colour ◽  
Pachytene Spermatocytes

The mammalian cell nucleus consists of numerous compartments involved in the regular unfolding of processes such as DNA replication and transcription, RNA maturation, protein synthesis and cell division. Knowledge is increasing of the relationships between high-order levels of chromatin organization and its spatial organization, and of how these relationships contribute to the various functions carried out in the nucleus. We have studied the spatial arrangement of mouse telocentric chromosomes 5, 11, 13, 15, 16 and 17, some of their metacentric Robertsonian derivatives, and X and Y chromosomes by whole chromosome painting in male germ (spermatogonia, pachytene spermatocytes and spermatids) and Sertoli cells of homozygous and heterozygous individuals. Using dual-colour fluorescence in situ hybridization we found that these chromosomes occupy specific nuclear territories in each cell type analysed. When chromosomes are present as Robertsonian metacentrics in the heterozygous state, that is, as Robertsonian metacentrics and their homologous telocentrics, differences in their nuclear positions are detectable: heterozygosity regularly produces a change in the nuclear position of one of the two homologous telocentrics in all the cell types studied. In the Robertsonian heterozygotes, the vast majority of the Sertoli cells show the sex chromosomes in a condensed state, whereas they appear decondensed in the Robertsonian homozygotes. As the Robertsonian heterozygosities we studied produce a chromosomally derived impairment of male germ-cell differentiation, we discuss the possibility that changes in chromosome spatial territories may alter some nuclear machinery (e.g., synapsis, differential gene expression) important for the correct unfolding of the meiotic process and for the proper functioning of Sertoli cells.

scholarly journals Temporal control of BMP signalling determines neuronal subtype identity in the dorsal neural tube

Development ◽  
2013 ◽  
Vol 140 (7) ◽  
pp. 1467-1474 ◽  
Author(s):  
S. Tozer ◽  
G. Le Dreau ◽  
E. Marti ◽  
J. Briscoe
Keyword(s):  
Neural Tube ◽  
Temporal Control ◽  
Dorsal Neural Tube ◽  
Neuronal Subtype ◽  
Bmp Signalling

Frequencies in vibrating wood – Does cell organization matter?

IAWA Journal ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 124-142
Author(s):  
Oliver Dünisch
Keyword(s):  
Spatial Organization ◽  
Ring Width ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Dominant Frequency ◽  
Fast Fourier Transformation ◽  
Frequency Spectra ◽  
Laser Sensors ◽  
Vibrating Plates ◽  
Dominant Frequencies

ABSTRACT The relationship between the spatial organization of different cell types, of the xylem rays, and of the tree rings and the frequencies in vibrating softwoods and hardwoods was studied under controlled conditions. In total, the frequencies in 1007 standardized vibrating plates from 16 softwoods and 74 hardwoods were analysed using high resolution laser sensors (accuracy ± 0.02 μm, sampling frequency 30 kHz) for vibration measurements. Overlapping frequencies within the frequency spectra were identified by means of Fast Fourier Transformation analysis. With regard to the number of distinct frequencies within the spectra, four different vibration types were identified: type 1–one dominant frequency within the frequency spectra; type 2-two dominant frequencies within the frequency spectra; type 3-three dominant frequencies within the frequency spectra; type 4-no dominant frequencies within the frequency spectra. The presence of distinct frequencies was correlated with a highly organized spatial arrangement of tracheids in softwoods, with a storied arrangement of the xylem rays in hardwoods, and with low variation in tree-ring width in both softwoods and hardwoods. The grid size for repetition in these xylem structures influenced the frequencies of the vibrating wood in absolute numbers. The results indicate that the analysis of the anatomical structure of the wood can contribute to the grading of timber for its vibration characteristics, which is of special interest for the selection of resonance wood for musical instruments.

Immuocytochemical analysis of spatial organization of photoreceptors and amacrine and ganglion cells in the tiger salamander retina

2004 ◽  
Vol 21 (2) ◽  
pp. 157-166 ◽  
Author(s):  
JIAN ZHANG ◽  
ZHUO YANG ◽  
SAMUEL M. WU
Keyword(s):  
Ganglion Cell ◽  
Spatial Organization ◽  
Ganglion Cells ◽  
Electrophysiological Study ◽  
Outer Nuclear Layer ◽  
Amacrine Cells ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Proximal Region ◽  
Dorsal Retina

In the present study, using double- or triple-label immunocytochemistry in conjunction with confocal microscopy, we aimed to examine the population and distribution of photoreceptors, GABAergic and glycinergic amacrine cells, and ganglion cells, which are basic but important parameters for studying the structure–function relationship of the salamander retina. We found that the outer nuclear layer (ONL) contained 82,019 ± 3203 photoreceptors, of which 52% were rods and 48% were cones. The density of photoreceptors peaked at ∼8000 cells/mm2 in the ventral and dropped to ∼4000 cells/mm2 in the dorsal retina. In addition, the rod/cone ratio was less than 1 in the central retina but larger than 1 in the periphery. Moreover, in the proximal region of the inner nuclear layer (INL3), the total number of cells was 50,576 ± 8400. GABAergic and glycinergic amacrine cells made up approximately 78% of all cells in this layer, including 43% GABAergic, 32% glycinergic, and 3% GABA/glycine colocalized amacrine cells. The density of these amacrine cells was ∼6500 cells/mm2 in the ventral and ∼3200 cells/mm2 in the dorsal area. The ratio of GABAergic to glycinergic amacrine cells was larger than 1. Furthermore, in the ganglion cell layer (GCL), among a total of 36,007 ± 2010 cells, ganglion cells accounted for 65.7 ± 1.5% of the total cells, whereas displaced GABAergic and glycinergic amacrine cells comprised about 4% of the cells in this layer. The ganglion cell density was ∼1800 cells/mm2 in the ventral and ∼600 cells/mm2 in the dorsal retina. Our data demonstrate that all three major cell types are not uniformly distributed across the salamander retina. Instead, they exhibit a higher density in the ventral than in the dorsal retina and their spatial arrangement is associated with the retinal topography. These findings provide a basic anatomical reference for the electrophysiological study of this species.

scholarly journals Cyclic AMP Signaling Functions as a Bimodal Switch in Sympathoadrenal Cell Development in Cultured Primary Neural Crest Cells

2000 ◽  
Vol 20 (9) ◽  
pp. 3004-3014 ◽  
Author(s):  
Matthew L. Bilodeau ◽  
Theresa Boulineau ◽  
Ronald L. Hullinger ◽  
Ourania M. Andrisani
Keyword(s):  
Cyclic Amp ◽  
Neural Crest ◽  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Cell Development ◽  
Camp Signaling ◽  
Camp Signaling Pathway ◽  
Trunk Neural Crest

ABSTRACT Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tissue culture, and they differentiate to a variety of neuronal and nonneuronal cell types. Earlier studies have determined that bone morphogenetic proteins (BMP-2, -4, and -7) and agents that elevate intracellular cyclic AMP (cAMP) stimulate the development of the sympathoadrenal (SA, adrenergic) lineage in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we characterized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture. We report that the cAMP signaling pathway modulates both positive and negative signals influencing the development of SA cells. Specifically, we show that moderate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. By contrast, robust activation of cAMP signaling opposes, even in the presence of BMP-2, SA cell development and the expression of the SA lineage-determining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bimodal regulator of SA cell development in neural crest cultures.

scholarly journals Notch signaling is a critical initiator of roof plate formation as revealed by the use of RNA profiling of the dorsal neural tube

2020 ◽  
Author(s):  
Shai Ofek ◽  
Sophie Wiszniak ◽  
Sarah Kagan ◽  
Markus Tondl ◽  
Quenten Schwarz ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Neural Tube ◽  
Transcriptome Analysis ◽  
Cell Types ◽  
Molecular Heterogeneity ◽  
Specific Cell ◽  
Rna Profiling ◽  
Dorsal Neural Tube ◽  
Roof Plate ◽  
Plate Formation

AbstractThe factors underlying establishment of the definitive roof plate (RP) and its segregation from neural crest (NC) and interneurons are unknown. We performed transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population. Collectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.Summary statementA new set of genes involved in Notch-dependent roof plate formation is unraveled by transcriptome analysis.

scholarly journals A spatial atlas of inhibitory cell types in mouse hippocampus

2018 ◽  
Author(s):  
Xiaoyan Qian ◽  
Kenneth D. Harris ◽  
Thomas Hauling ◽  
Dimitris Nicoloutsopoulos ◽  
Ana B. Muñoz-Manchado ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Memory Function ◽  
Expression Patterns ◽  
Ground Truth ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Cell System ◽  
Inhibitory Neurons ◽  
Hippocampal Area

Understanding the function of a tissue requires knowing the spatial organization of its constituent cell types. In the cerebral cortex, single-cell RNA sequencing (scRNA-seq) has revealed the genome-wide expression patterns that define its many, closely related cell types, but cannot reveal their spatial arrangement. Here we introduce probabilistic cell typing by in situ sequencing (pciSeq), an approach that leverages prior scRNA-seq classification to identify cell types using multiplexed in situ RNA detection. We applied this method to map the inhibitory neurons of hippocampal area CA1, a cell system critical for memory function, for which ground truth is available from extensive prior work identifying the laminar organization of subtly differing cell types. Our method confidently identified 16 interneuron classes, in a spatial arrangement closely matching ground truth. This method will allow identifying the spatial organization of fine cell types across the brain and other tissues.

scholarly journals Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

2016 ◽  
Vol 44 (4) ◽  
pp. 1117-1134 ◽  
Author(s):  
Pawina Jiramongkolchai ◽  
Philip Owens ◽  
Charles C. Hong
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Therapeutic Target ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Bone Morphogenetic Protein Pathway ◽  
Bmp Signalling ◽  
Unique Cell ◽  
The Impact

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

The role of bone morphogenetic proteins in vertebral development

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3607-3616 ◽  
Author(s):  
A.H. Monsoro-Burq ◽  
D. Duprez ◽  
Y. Watanabe ◽  
M. Bontoux ◽  
C. Vincent ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Neural Tube ◽  
Molecular Mechanisms ◽  
Spinous Process ◽  
Expression Patterns ◽  
Neural Tube Closure ◽  
Dorsal Neural Tube ◽  
Negative Effect ◽  
Msx Genes ◽  
Cell Growth And Differentiation

This study first shows a striking parallel between the expression patterns of the Bmp4, Msx1 and Msx2 genes in the lateral ridges of the neural plate before neural tube closure and later on, in the dorsal neural tube and superficial midline ectoderm. We have previously shown that the spinous process of the vertebra is formed from Msx1- and 2-expressing mesenchyme and that the dorsal neural tube can induce the differentiation of subcutaneous cartilage from the somitic mesenchyme. We show here that mouse BMP4- or human BMP2-producing cells grafted dorsally to the neural tube at E2 or E3 increase considerably the amount of Msx-expressing mesenchymal cells which are normally recruited from the somite to form the spinous process of the vertebra. Later on, the dorsal part of the vertebra is enlarged, resulting in vertebral fusion and, in some cases (e.g. grafts made at E3), in the formation of a ‘giant’ spinous process-like structure dorsally. In strong contrast, BMP-producing cells grafted laterally to the neural tube at E2 exerted a negative effect on the expression of Pax1 and Pax3 genes in the somitic mesenchyme, which then turned on Msx genes. Moreover, sclerotomal cell growth and differentiation into cartilage were then inhibited. Dorsalization of the neural tube, manifested by expression of Msx and Pax3 genes in the basal plate contacting the BMP-producing cells, was also observed. In conclusion, this study demonstrates that differentiation of the ventrolateral and dorsal parts of the vertebral cartilage is controlled by different molecular mechanisms. The former develops under the influence of signals arising from the floor plate-notochord complex. These signals inhibit the development of dorsal subcutaneous cartilage forming the spinous process, which requires the influence of BMP4 to differentiate.

A role for rhoB in the delamination of neural crest cells from the dorsal neural tube

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5055-5067 ◽  
Author(s):  
J.P. Liu ◽  
T.M. Jessell
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Bmp Signaling ◽  
Dorsal Neural Tube ◽  
Rho Family ◽  
Neural Crest Differentiation ◽  
Crest Cell

The differentiation of neural crest cells from progenitors located in the dorsal neural tube appears to involve three sequential steps: the specification of premigratory neural crest cell fate, the delamination of these cells from the neural epithelium and the migration of neural crest cells in the periphery. BMP signaling has been implicated in the specification of neural crest cell fate but the mechanisms that control the emergence of neural crest cells from the neural tube remain poorly understood. To identify molecules that might function at early steps of neural crest differentiation, we performed a PCR-based screen for genes induced by BMPs in chick neural plate cells. We describe the cloning and characterization of one gene obtained from this screen, rhoB, a member of the rho family GTP-binding proteins. rhoB is expressed in the dorsal neural tube and its expression persists transiently in migrating neural crest cells. BMPs induce the neural expression of rhoB but not the more widely expressed rho family member, rhoA. Inhibition of rho activity by C3 exotoxin prevents the delamination of neural crest cells from neural tube explants but has little effect on the initial specification of premigratory neural crest cell fate or on the later migration of neural crest cells. These results suggest that rhoB has a role in the delamination of neural crest cells from the dorsal neural tube.

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