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Results for “instructive signals”

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At least 163 records · Page 9Linked to original sources

PubMed2006

Endocannabinoids: a new family of lipid mediators involved in the regulation of neural cell development.

The endocannabinoids (eCBs) anandamide and 2-arachidonoylglycerol are important retrograde messengers that inhibit neurotransmitter release via presynaptic CB1 receptors. In addition, cannabinoids are known to modulate the cell death/survival decision of different neural cell types, leading to different outcomes that depend on the nature of the target cell and its proliferative/differentiation status. Thus, cannabinoids protect primary neurons, astrocytes and oligodendrocytes from apoptosis, whereas transformed glial cells are prone to apoptosis by cannabinoid challenge. Moreover, a potential role of the eCB system in neurogenesis and neural differentiation has been proposed. Recent research shows that eCBs stimulate neural progenitor proliferation and inhibit hippocampal neurogenesis in normal adult brain. Cannabinoids inhibit cortical neuron differentiation and promote glial differentiation. On the other hand, experiments with differentiated neurons have shown that cannabinoids also regulate neuritogenesis, axonal growth and synaptogenesis. These new observations support that eCBs constitute a new family of lipid signaling cues responsible for the regulation of neural progenitor proliferation and differentiation, acting as instructive proliferative signals through the CB1 receptor.

Animals↗

PubMed1997

The ins and outs of notch signaling.

The Notch gene encodes a cell surface protein that regulates cell fate choices in vertebrates and invertebrates. Given the wide variety of cell types influenced by Notch, it would seem that the signal relayed through Notch activation is not an instructive one per se. Rather, Notch signaling is thought to influence the cell's ability to respond to instructive signals responsible for specific cell fates. Expression and functional studies of Notch support this idea; however, the possibility of additional functions for Notch cannot be excluded. Much of what we know about the Notch signaling pathway comes from studies with Drosophila Notch and the Caenorhabditis elegans Notch-related genes lin-12 and glp-1. With the isolation of multiple vertebrate Notch genes we are beginning to understand and define Notch signaling in vertebrates as well. A number of excellent reviews have been published summarizing the current status of Notch/LIN-12/GLP-1 signaling in Drosophila and C. elegans, as well as recent findings with the vertebrate counterparts. Here I review the structure of the various Notch proteins and their putative ligands, and discuss possible interactions between Notch, its ligands, and other cellular components that affect Notch signal transduction. A role for Notch signaling during normal development and in disease processes is discussed in an accompanying review by T. Gridley (1997, Mol. Cell. Neurosci. 9: 103-108).

Animals↗

PubMed1991

Consistent arterial abnormalities associated with a variety of congenital malformations of the human lower limb.

A number of seemingly unrelated congenital deformities of the lower limb have been presented which include clubfoot, fibular deficiency, tibial aplasia, and diplopodia. Although the bony morphology in these limbs is quite different, they all share a strikingly similar arterial pattern, that being deficiency or absence of the anterior tibial artery, and of its derivative, the dorsal pedis artery. Since all of these diverse conditions share a similar aberrant arterial pattern, we suspect that the arterial changes are important in the pathogenesis of those conditions. Study of the soft tissue anatomy of these specimens suggests that the etiologic teratogenic event occurred early in embryonic development. In those limbs that contain the remnant of a missing structure, it is concluded that injury occurred after the mesenchyme was instructed to form that structure. These are termed "post-specification" defects. In those circumstances where limb duplication occurs, the injury affected the signal before instruction of mesenchyme to develop into a specific structure was completed and these abnormalities are termed "pre-specification" malformations. The musculotendenous and neurologic abnormalities seem to be reactive to the pre-existing bony pattern.

Angiography↗

PubMed2000

Stem cells: You make me feel so glial.

The signals that instruct neural stem cells to differentiate into glia have long proved elusive. Surprising new evidence suggests that this role could be fulfilled by Notch signalling, previously thought to be a general inhibitor of stem cell differentiation.

Animals↗

PubMed1983

[Participation of the orienting-exploratory reaction in the formation of a secondary signal association system in lecture instruction].

The close correlation between the skin galvanic reaction (SGR) and the process of formation of scientific knowledge (abstract-logical temporal connections) has been shown by using SGR for the determination of the secondary signal system activity. Rather a high level of each student's SGR is kept during the whole lecture. The more active the student's SGR is mobilized the more efficient the scientific knowledge is learnt.

Association Learning↗

PubMed1996

Suppression of apoptosis during cytokine deprivation of 32D cells is not sufficient to induce complete granulocytic differentiation.

The role of cytokines in the control of hematopoietic cell differentiation remains controversial. Two general models for the cytokine control of hematopoietic differentiation have been proposed. In the stochastic model, cytokines provide proliferative and survival signals to the differentiating hematopoietic cell, but they do not provide specific lineage commitment signals. In the instructive model, cytokines transmit specific signals to multipotent hematopoietic cells, thereby directing lineage commitment. To distinguish between these two models with respect to granulocyte colony-stimulating factor (G-CSF) and granulocytic differentiation, we used the 32Dcl3 cell line, which is capable of differentiating into granulocytes in response to G-CSF, 32D cells transfected with either bcl-2 or bcl-XL showed prolonged survival in medium containing no cytokine supplement. Cells surviving in these cultures developed the segmented nuclei characteristic of mature neutrophils. However, no induction of myeloperoxidase activity or increase in cathepsin G transcripts were detected. These data support a hybrid model for the role of G-CSF in granulocytic differentiation; although some features of granulocytic differentiation, namely nuclear segmentation, do not require G-CSF and appear therefore to be preprogrammed in 32D cells, the complete maturation of these cells to granulocytes appears to be dependent on G-CSF.

Animals↗

PubMedDate not supplied

Specificity of signaling by hematopoietic cytokine receptors: instructive versus permissive effects.

The helical cytokines constitute a family of proteins with a common three-dimensional structure. They exert a wide variety of biological effects with a preference for the hematopoietic system. The effects of helical cytokines are mediated by cell surface receptors, which belong to the cytokine receptor superfamily and signal by activating cytoplasmic tyrosine kinases of the Janus kinase (Jak) family and other downstream signaling pathways. The relevance of each of these pathways for eliciting a specific cellular response remains to be determined. This review will focus on cytokine receptors which play a role in the regulation of hematopoiesis and summarize data the address the question how specificity of signaling is achieved.

Animals↗

PubMed1994

Neurotrophic factors and their receptors.

Development of the nervous system depends on signals that instruct neurons when to divide, differentiate, survive, or die. There are now two known distinct classes of factors noted for their neurotrophic activities-the family of factors collectively known as the neurotrophins, and ciliary neurotrophic factor. Neurotrophin-mediated signaling pathways initiate by autophosphorylation of Trk receptors, which are receptor tyrosine kinases similar to the receptors for traditional growth factors such as fibroblast growth factor. In contrast, ciliary neurotrophic factor employs a receptor system that shares components with the receptor complexes for a subclass of distantly related hematopoietic cytokines. These two distinct classes of neurotrophic factors, utilizing distinct signaling pathways, can interact to effect the growth and differentiation of neuronal progenitors during neuropoiesis in a way analogous to that exhibited by the cytokines during hematopoiesis.

Animals↗

PubMed1993

Localized hedgehog activity controls spatial limits of wingless transcription in the Drosophila embryo.

Cell patterning in the body segments of the Drosophila embryo requires activity of the segment polarity genes, a molecularly heterogeneous group defined by a generic mutant phenotype. Two of these genes, wingless (wg) and hedgehog (hh), encode proteins that enter the secretory pathway, implicating them as signals that instruct the fates of neighbouring cells. Genetic analysis has identified wg transcription as one of the targets of hh activity and it has been suggested that the spatial control of wg expression depends on the limited range of the hh signal and the differential competence of responding cells. I have tested this model by driving ubiquitous expression of the hh gene using the Hsp70 promoter. Here I report that, as predicted, this causes the ectopic activation of wg in only a subset of the cells of each parasegment. Using another target of hh activity as a probe, I demonstrate that the competence of cells to express wg is independent of their ability to receive the hh signal. Finally, I show that wg activation requires the function of the segment polarity gene fused, suggesting that the putative hh signal is transduced by the serine/threonine kinase that fused encodes.

Animals↗

PubMed2002

Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics.

Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVM(light). Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms.

Algorithms↗

PubMed2002

Subdivision of the Drosophila wing imaginal disc by EGFR-mediated signaling.

Growth and patterning of the Drosophila wing imaginal disc depends on its subdivision into dorsoventral (DV) compartments and limb (wing) and body wall (notum) primordia. We present evidence that both the DV and wing-notum subdivisions are specified by activation of the Drosophila Epidermal Growth Factor Receptor (EGFR). We show that EGFR signaling is necessary and sufficient to activate apterous (ap) expression, thereby segregating the wing disc into D (ap-ON) and V (ap-OFF) compartments. Similarly, we demonstrate that EGFR signaling directs the expression of Iroquois Complex (Iro-C) genes in prospective notum cells, rendering them distinct from, and immiscible with, neighboring wing cells. However, EGFR signaling acts only early in development to heritably activate ap, whereas it is required persistently during subsequent development to maintain Iro-C gene expression. Hence, as the disc grows, the DV compartment boundary can shift ventrally, beyond the range of the instructive EGFR signal(s), in contrast to the notum-wing boundary, which continues to be defined by EGFR input.

Animals↗

PubMed1979

Patient-initiated transtelephone transmission of electrocardiographic signals in the diagnosis of arrhythmias.

Thirty-one patients who had complained of recurrent palpitations were given transtelephone transmitters of electrocardiographic signals and instructed to use the transmitters while they were having symptoms. From the transcribed electrocardiograms sinus tachycardia was documented in 12 patients, paroxysmal atrial tachycardia in 7, atrial fibrillation in 4, atrial flutter in 3, frequent ventricular premature beats in 4 and ventricular tachycardia in 1. Patient-initiated transtelephone transmission of electrocardiographic signals was found to be an effective means of documenting the nature of symptomatic paroxysmal tachycardia.

Adolescent↗

PubMed1995

Positional signaling by hedgehog in Drosophila imaginal disc development.

We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary.

Alleles↗

PubMed1998

Absence of cytokine receptor-dependent specificity in red blood cell differentiation in vivo.

Erythropoietin (EPO) is required for red blood cell development, but whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric receptors were constructed by replacing the cytoplasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for terminal differentiation of erythrocytes. Furthermore, we found that cellular context can influence cytokine receptor signaling.

3T3 Cells↗

PubMed2006

Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb.

Establishment of limb innervation by motor neurons involves a series of hierarchical axon guidance decisions by which motor-neuron subtypes evaluate peripheral guidance cues and choose their axonal trajectory. Earlier work indicated that the pathway into the dorsal limb by lateral motor column (LMC[l]) axons requires the EphA4 receptor, which mediates repulsion elicited by ephrinAs expressed in ventral limb mesoderm. Here, we implicate glial-cell-line-derived neurotrophic factor (GDNF) and its receptor, Ret, in the same guidance decision. In Gdnf or Ret mutant mice, LMC(l) axons follow an aberrant ventral trajectory away from dorsal territory enriched in GDNF, showing that the GDNF/Ret system functions as an instructive guidance signal for motor axons. This phenotype is enhanced in mutant mice lacking Ret and EphA4. Thus, Ret and EphA4 signals cooperate to enforce the precision of the same binary choice in motor-axon guidance.

Animals↗

PubMed1984

Comfortable loudness levels for speech: effects of signal-to-noise ratios and instructions.

The effect of S/N from +20 to -10 db on loudness levels of connected discourse with or without background cafeteria noise was investigated for one set of instructions sampling the most comfortable loudness level (MCLL) and a second set sampling the upper limit of CLL. Normal young adults (N:16) showed no significant differences for either set of instructions in quiet or from 20 to 0 db S/N but mn MCLL was about 5 db lower at -10 db. Elderly hearing-aid wearers (N:10, mn age: 77 yrs) yielded mn differences across S/N of less than 5 db for either set of instructions. No data indicate that the speech CLL accurately predicts optimal hearing-aid gain, while the literature indicates that occasionally the desired maximum intelligibility frequently is not obtained at the MCLL. We question whether MCLL for speech justifies its measurement. A discussion is presented of the Comfort Level Method of adjusting gain in hearing-aid evaluations and a perhaps preferable Threshold Level Method in which the test stimulus is presented at a level corresponding to the predicted threshold and the aid's volume control is adjusted until S just perceives the signal.

Adult↗

PubMed2004

Oxidative stress signalling in Alzheimer's disease.

Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in the disease. Indeed, that oxidative mechanisms are involved in the cell loss and other neuropathology associated with AD is evidenced by the large number of metabolic signs of oxidative stress as well as by markers of oxidative damage. However, what is intriguing is that oxidative damage decreases with disease progression, such that levels of markers of rapidly formed oxidative damage, which are initially elevated, decrease as the disease progresses to advanced AD. This finding, along with the compensatory upregulation of antioxidant enzymes found in vulnerable neurons in AD, indicates that reactive oxygen species (ROS) not only cause damage to cellular structures but also provoke cellular responses. Mammalian cells respond to extracellular stimuli by transmitting intracellular instructions by signal transduction cascades to coordinate appropriate responses. Therefore, not surprisingly stress-activated protein kinase (SAPK) pathways, pathways that are activated by oxidative stress, are extensively activated during AD. In this paper, we review the evidence of oxidative stress and compensatory responses that occur in AD with a particular focus on the roles and mechanism of activation of SAPK pathways.

Alzheimer Disease↗

PubMed1998

The molecular ZPA.

Signals that instruct the developing limb bud mesenchyme to form the appropriate elements along the anterior posterior axis emanate from the zone of polarizing activity (ZPA). Studies of the last five years have illustrated that the Sonic hedgehog (Shh) protein mediates the activities of the ZPA. This review will focus on three aspects of the ZPA biology. We will address induction of the ZPA in terms of the factors required for activation and maintenance of Shh expression in the posterior limb bud mesenchyme and the evidence for negative regulatory mechanisms that prevent inappropriate Shh expression. Second, we will discuss the current understanding of Shh processing and transduction of the Shh signal, inferring much from the elegant studies on Drosophila Hedgehog (Hh) protein. Finally, we will address the interpretation of the secreted Shh signal by the limb bud mesenchyme that leads to a predictable morphological response.

Animals↗