Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cells ◽  
Dorsoventral Patterning ◽  
Cellular Mechanisms ◽  
Cell Position

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

scholarly journals Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Zika Virus ◽  
Developmental Stages ◽  
Cell Types ◽  
Neural Cells ◽  
Zikv Infection ◽  
Axonal Pathology ◽  
Time Frames

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro

Development ◽  
1997 ◽  
Vol 124 (7) ◽  
pp. 1313-1322 ◽  
Author(s):  
H. Sasaki ◽  
C. Hui ◽  
M. Nakafuku ◽  
H. Kondoh
Keyword(s):  
Binding Site ◽  
Neural Tube ◽  
Floor Plate ◽  
Signalling Pathway ◽  
Axonal Guidance ◽  
Critical Event ◽  
Enhancer Activity ◽  
Gli Proteins

The floor plate plays important roles in ventral pattern formation and axonal guidance within the neural tube of vertebrate embryos. A critical event for floor plate development is the induction of a winged helix transcription factor, Hepatocyte Nuclear Factor-3beta (HNF-3beta). The enhancer for floor plate expression of HNF-3beta is located 3′ of the transcription unit and consists of multiple elements. HNF-3beta induction depends on the notochord-derived signal, Sonic hedgehog (Shh). Genetic analysis in Drosophila has led to the identification of genes involved in the Hh signalling pathway, and cubitus interruptus (ci), encoding a protein with five zinc finger motifs, was placed downstream. In the present work, we test the involvement of Gli proteins, the mouse homologues of Ci, in activation of the floor plate enhancer of HNF-3beta. Transgenic analysis shows that a Gli-binding site is required for the activity of the minimal floor plate enhancer of HNF-3beta in vivo. Three Gli genes are differentially expressed in the developing neural tube. Gli expression is restricted to the ventral part, while Gli2 and Gli3 are expressed throughout the neural tube and dorsally, respectively. Strong Gli and Gli2, and weak Gli3 expressions transiently overlap with HNF-3beta at the time of its induction. Consistent with ventrally localized expression, Gli expression can be up-regulated by Shh in a cell line. Finally, the Gli-binding site acts as a Shh responsive element, and human GLI, but not GLI3, can activate this binding site in tissue culture. Taken together, these findings suggest that Gli, and probably also Gli2, are good candidates for transcriptional activators of the HNF-3beta floor plate enhancer, and the binding site for Gli proteins is a key element for response to Shh signalling. These results also support the idea that Gli/Ci are evolutionary conserved transcription factors in the Hedgehog signalling pathway.

scholarly journals Genetic neuroscience of mammalian learning and memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 787-795 ◽  
Author(s):  
Susumu Tonegawa ◽  
Kazu Nakazawa ◽  
Matthew A. Wilson
Keyword(s):  
Cell Types ◽  
Genetically Engineered ◽  
Mouse Strains ◽  
Cellular Mechanisms ◽  
Genetic Manipulations ◽  
Adult Mice ◽  
Multiple Levels ◽  
Primary Research Interest

Our primary research interest is to understand the molecular and cellular mechanisms on neuronal circuitry underlying the acquisition, consolidation and retrieval of hippocampus-dependent memory in rodents. We study these problems by producing genetically engineered (i.e. spatially targeted and/or temporally restricted) mice and analysing these mice by multifaceted methods including molecular and cellular biology, in vitro and in vivo physiology and behavioural studies. We attempt to identify deficits at each of the multiple levels of complexity in specific brain areas or cell types and deduce those deficits that underlie specific learning or memory. We will review our recent studies on the acquisition, consolidation and recall of memories that have been conducted with mouse strains in which genetic manipulations were targeted to specific types of cells in the hippocampus or forebrain of young adult mice.

scholarly journals Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch

2019 ◽  
Vol 116 (45) ◽  
pp. 22624-22634 ◽  
Author(s):  
Kotaro Fujimaki ◽  
Ruoyan Li ◽  
Hengyu Chen ◽  
Kimiko Della Croce ◽  
Hao Helen Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Signature ◽  
Cell Types ◽  
The Body ◽  
Cellular Mechanisms ◽  
Lysosomal Function ◽  
Quiescent Cells ◽  
Common Transition

The reactivation of quiescent cells to proliferate is fundamental to tissue repair and homeostasis in the body. Often referred to as the G0 state, quiescence is, however, not a uniform state but with graded depth. Shallow quiescent cells exhibit a higher tendency to revert to proliferation than deep quiescent cells, while deep quiescent cells are still fully reversible under physiological conditions, distinct from senescent cells. Cellular mechanisms underlying the control of quiescence depth and the connection between quiescence and senescence are poorly characterized, representing a missing link in our understanding of tissue homeostasis and regeneration. Here we measured transcriptome changes as rat embryonic fibroblasts moved from shallow to deep quiescence over time in the absence of growth signals. We found that lysosomal gene expression was significantly up-regulated in deep quiescence, and partially compensated for gradually reduced autophagy flux. Reducing lysosomal function drove cells progressively deeper into quiescence and eventually into a senescence-like irreversibly arrested state; increasing lysosomal function, by lowering oxidative stress, progressively pushed cells into shallower quiescence. That is, lysosomal function modulates graded quiescence depth between proliferation and senescence as a dimmer switch. Finally, we found that a gene-expression signature developed by comparing deep and shallow quiescence in fibroblasts can correctly classify a wide array of senescent and aging cell types in vitro and in vivo, suggesting that while quiescence is generally considered to protect cells from irreversible arrest of senescence, quiescence deepening likely represents a common transition path from cell proliferation to senescence, related to aging.

Induction of floor plate differentiation by contact-dependent, homeogenetic signals

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 205-218 ◽  
Author(s):  
M. Placzek ◽  
T.M. Jessell ◽  
J. Dodd
Keyword(s):  
Axon Guidance ◽  
Neural Tube ◽  
Floor Plate ◽  
Cell Patterning ◽  
Neural Plate ◽  
Neural Cells ◽  
Cellular Mechanisms ◽  
Prechordal Mesoderm ◽  
Specific Antigens ◽  
Inductive Signals

The floor plate is located at the ventral midline of the neural tube and has been implicated in neural cell patterning and axon guidance. To address the cellular mechanisms involved in floor plate differentiation, we have used an assay that monitors the expression of floor-plate-specific antigens in neural plate explants cultured in the presence of inducing tissues. Contact-mediated signals from both the notochord and the floor plate act directly on neural plate cells to induce floor plate differentiation. Floor plate induction is initiated medially by a signal from the notochord, but appears to be propagated to more lateral cells by homeogenetic signals that derive from medial floor plate cells. The response of neural plate cells to inductive signals declines with embryonic age, suggesting that the mediolateral extent of the floor plate is limited by a loss of competence of neural cells. The rostral boundary of the floor plate at the midbrain-forebrain junction appears to result from the lack of inducing activity in prechordal mesoderm and the inability of rostral neural plate cells to respond to inductive signals.

scholarly journals DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members

2018 ◽  
Vol 115 (43) ◽  
pp. E10216-E10224 ◽  
Author(s):  
Andrew M. Garrett ◽  
Andre Khalil ◽  
David O. Walton ◽  
Robert W. Burgess
Keyword(s):  
Cell Adhesion ◽  
Neural Development ◽  
Individual Cell ◽  
Cell Types ◽  
Mouse Retina ◽  
Cell Level ◽  
The Individual ◽  
Cadherin Superfamily

During neural development, self-avoidance ensures that a neuron’s processes arborize to evenly fill a particular spatial domain. At the individual cell level, self-avoidance is promoted by genes encoding cell-surface molecules capable of generating thousands of diverse isoforms, such as Dscam1 (Down syndrome cell adhesion molecule 1) in Drosophila. Isoform choice differs between neighboring cells, allowing neurons to distinguish “self” from “nonself”. In the mouse retina, Dscam promotes self-avoidance at the level of cell types, but without extreme isoform diversity. Therefore, we hypothesize that DSCAM is a general self-avoidance cue that “masks” other cell type-specific adhesion systems to prevent overly exuberant adhesion. Here, we provide in vivo and in vitro evidence that DSCAM masks the functions of members of the cadherin superfamily, supporting this hypothesis. Thus, unlike the isoform-rich molecules tasked with self-avoidance at the individual cell level, here the diversity resides on the adhesive side, positioning DSCAM as a generalized modulator of cell adhesion during neural development.

Prevention of spinal neural tube defects in the mouse embryo by growth retardation during neurulation

Development ◽  
1988 ◽  
Vol 104 (2) ◽  
pp. 297-303 ◽  
Author(s):  
A.J. Copp ◽  
J.A. Crolla ◽  
F.A. Brook
Keyword(s):  
Cell Proliferation ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Growth Retardation ◽  
Cell Types ◽  
Growing Cell ◽  
Posterior Neuropore ◽  
Curly Tail

Homozygous mutant curly tail mouse embryos developing spinal neural tube defects (NTD) exhibit a cell-type-specific abnormality of cell proliferation that affects the gut endoderm and notochord but not the neuroepithelium. We suggested that spinal NTD in these embryos may result from the imbalance of cell proliferation rates between affected and unaffected cell types. In order to test this hypothesis, curly tail embryos were subjected to influences that retard growth in vivo and in vitro. The expectation was that growth of unaffected rapidly growing cell types would be reduced to a greater extent than affected slowly growing cell types, thus counteracting the genetically determined imbalance of cell proliferation rates and leading to normalization of spinal neurulation. Food deprivation of pregnant females for 48 h prior to the stage of posterior neuropore closure reduced the overall incidence of spinal NTD and almost completely prevented open spina bifida, the most severe form of spinal NTD in curly tail mice. Analysis of embryos earlier in gestation showed that growth retardation acts by reducing the incidence of delayed neuropore closure. Culture of embryos at 40.5 degrees C for 15–23 h from day 10 of gestation, like food deprivation in vivo, also produced growth retardation and led to normalization of posterior neuropore closure. Labelling of embryos in vitro with [3H]thymidine for 1 h at the end of the culture period showed that the labelling index is reduced to a greater extent in the neuroepithelium than in other cell types in growth-retarded embryos compared with controls cultured at 38 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4855-4866 ◽  
Author(s):  
K.F. Liem ◽  
T.M. Jessell ◽  
J. Briscoe
Keyword(s):  
Neural Tube ◽  
Progenitor Cell ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Neural Cells ◽  
Cell Identity ◽  
Neuronal Fate ◽  
Ventral Neural Tube

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-to-ventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube.

scholarly journals ModelingIn VitroCellular Responses to Silver Nanoparticles

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Dwaipayan Mukherjee ◽  
Steven G. Royce ◽  
Srijata Sarkar ◽  
Andrew Thorley ◽  
Stephan Schwander ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cell Types ◽  
Engineered Nanoparticles ◽  
Mrna Levels ◽  
Cellular Interactions ◽  
Cellular Mechanisms ◽  
Nanoparticle Transport ◽  
Cell Culture Systems

Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types.In vitrocell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systemsin vitro, to develop a mechanistic mathematical model that can support analysis and prediction ofin vivoeffects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized usingin vitromeasurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includesin vitrocellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based onin vitromeasurements, and provides a “stepping stone” for the development of more advancedin vivomodels that will incorporate additional cellular and NP interactions.

Neural Development by Transplanted Human Embryonal Carcinoma Stem Cells Expressing Green Fluorescent Protein

2005 ◽  
Vol 14 (6) ◽  
pp. 339-351 ◽  
Author(s):  
R. Stewart ◽  
M. Lako ◽  
G. M. Horrocks ◽  
S. A. Przyborski
Keyword(s):  
Stem Cells ◽  
Green Fluorescent Protein ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Embryonal Carcinoma ◽  
Fluorescent Protein ◽  
Cell Types ◽  
Green Fluorescent

For many years, researchers have investigated the fate and potential of neuroectodermal cells during the development of the central nervous system. Although several key factors that regulate neural differentiation have been identified, much remains unknown about the molecular mechanisms that control the fate and specification of neural subtypes, especially in humans. Human embryonal carcinoma (EC) stem cells are valuable research tools for the study of neural development; however, existing in vitro experiments are limited to inducing the differentiation of EC cells into only a handful of cell types. In this study, we developed and characterized a novel EC cell line (termed TERA2.cl.SP12-GFP) that carries the reporter molecule, green fluorescent protein (GFP). We demonstrate that TERA2.cl.SP12-GFP stem cells and their differentiated neural derivatives constitutively express GFP in cells grown both in vitro and in vivo. Cellular differentiation does not appear to be affected by insertion of the transgene. We propose that TERA2.cl.SP12-GFP cells provide a valuable research tool to track the fate of cells subsequent to transplantation into alternative environments and that this approach may be particularly useful to investigate the differentiation of human neural tissues in response to local environmental signals.

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