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Results for “instructive signals”

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At least 109 records · Page 6Linked to original sources

PubMed2002

Comparison of the expression patterns of several fibroblast growth factors during chick gastrulation and neurulation.

The fibroblast growth factor family consists of a large number of secreted polypeptide growth factors. The developmental importance of the family has been highlighted in many studies, which serve to underscore their role as local instructive signals directing diverse processes in the developing embryo. We wished to characterize and compare the expression patterns of nine members of the fibroblast growth factor family in the chick embryo. In this study, we survey the expression patterns of fgf-2, -3, -4, -8, -10, -12, -13, -14 and -18 during gastrula and neurula stages (Hamburger and Hamilton stages: 4-13). As well as providing a comparison of the expression patterns of those fibroblast growth factors already published, we provide new data on the expression patterns of some of these genes at early stages.

Animals↗

PubMed2004

Expression of neuronal markers suggests heterogeneity of chick sympathoadrenal cells prior to invasion of the adrenal anlagen.

We have analyzed the distribution of neural crest-derived precursors and the expression of catecholaminergic and neuronal markers in developing adrenal tissue of chick embryos. Undifferentiated neural crest cells are found in presumptive adrenal regions from embryonic day 3 (E3) onward. An increasing proportion of cells expressing tyrosine hydroxylase (TH) mRNA indicates catecholaminergic differentiation of precursors not only in primary sympathetic ganglia, but also in presumptive adrenal regions. Whereas precursors and differentiating cells show mesenchymal distribution until E5, discrete adrenal anlagen form during E6. Even during E5, catecholaminergic cells with low or undetectable neurofilament M (NF-M) mRNA expression prevail in positions at which adrenal anlagen become distinct during E6. The predominance of TH-positive and NF-M-negative cells is maintained throughout embryogenesis in adrenal tissue. RNA encoding SCG10, a pan-neuronal marker like NF-M, is strongly expressed throughout adrenal anlagen during E6 but is found at reduced levels in chromaffin cells compared with neuronal cells at E15. Two additional neuronal markers, synaptotagmin 1 and neurexin 1, are expressed at low to undetectable levels in developing chromaffin cells throughout embryogenesis. The developmental regulation of neuronal markers shows at least three different patterns among the four mRNAs analyzed. Importantly, there is no generalized downregulation of neuronal markers in developing adrenal anlagen. Thus, our observations question the classical concept of chromaffin differentiation from a common sympathoadrenal progenitor expressing neuronal properties and suggest alternative models with changing instructive signals or separate progenitor populations for sympathetic neuronal and chromaffin endocrine cells.

Adrenal Glands↗

PubMed1991

Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage.

Immature thymocytes, which coexpress CD4 and CD8, give rise to mature CD4+CD8- and CD4-CD8+ T cells. Only those T cells that recognize self-MHC are selected to mature, a process known as positive selection. The specificity of the T cell antigen receptor (TCR) for class I or class II MHC influences the commitment to a CD4 or CD8 lineage. This may occur by a directed mechanism or by stochastic commitment followed by a selection step that allows only CD8+, class I-specific and CD4+, class II-specific cells to survive. We have generated a mouse line expressing a CD8 transgene under the control of the T cell-specific CD2 regulatory sequences. Although constitutive CD8 expression does not affect thymic selection of CD4+ cells, selection of a class I-specific TCR in the CD8 subset is substantially improved. This outcome is consistent with a model for positive selection in which selection occurs at a developmental stage in which both CD4 and CD8 are expressed, and positive selection by class I MHC generates an instructive signal that directs differentiation to a CD8 lineage.

Animals↗

PubMed1995

Hydroxyindole-O-methyltransferase gene expression in the pineal gland of chicken embryo: development of messenger RNA levels and regulation by serum.

Hydroxyindole-O-methyltransferase (HIOMT), the enzyme which catalyzes the final step of melatonin biosynthesis, constitutes a marker of the functional differentiation of pineal cells. In addition, a day/night rhythm of HIOMT mRNA concentration, previously described in the chicken pineal gland [6], would suggest that HIOMT gene transcription is one output of the circadian system that controls pineal function. The study sought to monitor the developmental expression of HIOMT mRNA in the chick pineal gland and to investigate a possible role of instructive signals in this differentiation process. RT-PCR analysis indicated that HIOMT mRNA is expressed at embryonic day 8 (E8). At E12, HIOMT mRNA became detectable on northern blots and traces of HIOMT activity could be measured. HIOMT mRNA concentration increased 100-fold between E14 and day 10 post-hatch, then levelled off. A day/night rhythm of HIOMT mRNA concentration was readily observed in the pineal gland of 2-day-old chicks. Pineal glands isolated on minimum culture medium at E11 stopped developing HIOMT gene expression. However, the addition of serum to the culture medium restored HIOMT mRNA concentration to the levels observed in vivo. The data suggest that the functional differentiation of melatoninergic cells observed during the second week of embryonic life may be controlled [correction of controled] by serum factors.

Acetylserotonin O-Methyltransferase↗

PubMed1986

Role of the monkey substantia nigra pars reticulata in orienting behaviour and visually triggered arm movements.

The role of the substantia nigra pars reticulata (SNpr) has been studied in the head-free monkey during orienting behaviour in response to visual instruction signals triggering head positioning and conditioned arm movement. During the behavioural responses we recorded the electromyographic activities of neck muscles and triceps brachii, head movement, horizontal electrooculogram and single unit activity of SNpr neurons. Activity of 38 neurons located in the medial part of SNpr were analysed during the visuo-motor task. Forty percent of these units showed a moderate decrease in tonic firing rate during postural preparation preceding the orientation toward eccentric visual signal. This decrease, unrelated with saccadic eye movements per se, was followed by a marked pause observed when the rewarded stimulus was switched on and the conditioned arm movement was executed to get the reward. These data suggest that the pause in discharge of these SNpr neurons are time locked with behaviourally relevant visual stimuli and/or appropriate motor responses.

Animals↗

PubMed2004

Perinatal applications of neural stem cells.

The brain, unlike many tissues, has a limited capacity for self-repair and so there has been great interest in the possibility of transplanting neural cells to replace those lost through injury or disease. Encouraging research in humans is already underway examining the possibility of neural cell replacement in adult neurodegenerative conditions such as Parkinson's disease and Huntington disease. In addition, experiments exploring neural stem cell replacement in rodent models of acute stroke, demyelination and spinal cord injury have demonstrated functional improvements in treated animals. When considering perinatal neural stem cell therapy, it should not be overlooked that the immature, developing brain might provide a more favourable environment for stem cell integration. However, considerable advances need to be made both in understanding the basic biology of neural stem cells, including the instructive signals that determine their proliferation and differentiation, and in characterising their responses when transplanted in a damaged or diseased area of the brain.

Central Nervous System↗

PubMed2005

Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin.

BACKGROUND: Lactobacilli are probiotic bacteria that are frequently tested in the management of allergic diseases or gastroenteritis. It is hypothesized that these probiotics have immunoregulatory properties and promote mucosal tolerance, which is in part mediated by regulatory T cells (Treg cells). On the basis of pathogenic or tissue-specific priming, dendritic cells (DC) acquire different T cell-instructive signals and drive the differentiation of naive T H cells into either T H 1, T H 2, or regulatory effector T cells. OBJECTIVE: We studied in what way different species of lactobacilli prime human DCs for their ability to drive Treg cells. METHODS: Human monocyte-derived DCs were cultured in vitro with lactobacilli of different species. RESULTS: Two different species of lactobacilli, Lactobacillus reuteri and Lactobacillus casei , but not Lactobacillus plantarum, prime monocyte-derived DCs to drive the development of Treg cells. These Treg cells produced increased levels of IL-10 and were capable of inhibiting the proliferation of bystander T cells in an IL-10-dependent fashion. Strikingly, both L reuteri and L casei , but not L plantarum , bind the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Blocking antibodies to DC-SIGN inhibited the induction of the Treg cells by these probiotic bacteria, stressing that ligation of DC-SIGN can actively prime DCs to induce Treg cells. CONCLUSIONS: The targeting of DC-SIGN by certain probiotic bacteria might explain their beneficial effect in the treatment of a number of inflammatory diseases, including atopic dermatitis and Crohn's disease.

Antigens, CD↗

PubMed2006

Expression of marker genes during early ear development in medaka.

Induction of the otic placode involves a number of regulatory interactions. Early studies revealed that the induction of this program is initiated by instructive signals from the mesendoderm as well as from the adjacent hindbrain. Further investigations on the molecular level identified in zebrafish Fgf3, Fgf8, Foxi1, Pax8, Dlx3b and Dlx4b genes as key players during the induction phase. Thereafter an increasing number of genes participates in the regulatory interactions finally resulting in a highly structured sensory organ. Based on data from zebrafish we selected medaka genes with presumptive functions during early ear development for an expression analysis. In addition we isolated Foxi1 and Dlx3b gene fragments from embryonic cDNA. Altogether we screened the spatio-temporal distribution of more than 20 representative marker genes for otic development in medaka embryos, with special emphasis on the early phases. Whereas the spatial distribution of these genes is largely conserved between medaka and zebrafish, our comparative analysis revealed several differences, in particular for the timing of expression.

Animals↗

PubMed2005

Role of NRSF/REST in the molecular mechanisms regulating neural-specific expression of trkC/neurotrophin-3 receptor gene.

The processes of differentiation and development of neurons involve the induction of neuron-specific genes by instructive signals with subsequent neurotrophic factor-driven survival and functional maturation. We have previously shown that bone morphogenetic protein-2 (BMP2) and retinoic acid synergistically induce the responsiveness of developing sympathetic neurons to neurotrophic factors, neurotrophin 3 (NT-3), and GDNF by upregulating corresponding receptors concomitantly with the induction of other neuron-specific genes including BRINP1, a neuron-specific cell-cycle regulatory protein. In the present study, we analyzed transcriptional mechanisms regulating the neuron-specific expression of TrkC/NT-3 receptor gene. TrkC gene contains at least four NRSE/RE-1 (neuron-restrictive silencing element/repressor element 1)-like elements (TrkC-NRSE A-D). Consequently, we found that in non-neuronal cells, neuron-restrictive silencing factor (NRSF) acts on TrkC-NRSE D located at the downstream of exon 3 to suppress the promoter activity of TrkC gene in a manner similar to the mechanism of NRSF suppressing BRINP1 transcription. In contrast, in neuronal cells, the biological activity of NRSF on TrkC was suppressed. From these observations, molecular mechanisms regulating the expression of neuron-specific genes via NRSE during neuronal differentiation are discussed.

Animals↗

PubMed2004

Electroencephalographic nogo potentials in a no-movement context: the case of motor imagery in humans.

The nogo potentials (N2/P3) were studied in a precuing auditory reaction time task in human subjects who had to either perform a button-press response (Press condition) or imagine they were performing it (Imagine condition). In the full precue condition (the subjects knew in advance which response they had to perform/imagine), in 25% of the trials, a nogo signal instructed the subject not to perform or not to imagine the prepared action. Clear N2/P3 components were obtained on nogo trials on the Press trials, but also on the Imagine ones: the N2 was of similar amplitude in both conditions, whereas the P3 was of smaller amplitude in the Imagine condition. The presence of nogo potential in motor imagery is discussed in terms of the functional significance of the N2/P3 complex.

Electroencephalography↗

PubMed2005

Patterning molecules; multitasking in the nervous system.

Classical patterning molecules that were previously implicated in controlling cell fate choices in the nervous system have recently been shown to play additional roles in axon guidance and synaptogenesis. Bone morphogenetic proteins (BMPs), Sonic hedgehog (Shh), Wnts, and fibroblast growth factors (FGFs) all participate in multiple acts of controlling neuronal circuit assembly. Depending on the cellular context, they can provide instructive signals at the growth cone or synapse or alternatively can elicit responses in the nucleus initiating transcriptional changes. Differences in signal transduction pathways may contribute to the diversity of the functional repertoire of these versatile molecules.

Animals↗

PubMed2003

Mechanisms of ectodermal organogenesis.

All ectodermal organs, e.g. hair, teeth, and many exocrine glands, originate from two adjacent tissue layers: the epithelium and the mesenchyme. Similar sequential and reciprocal interactions between the epithelium and mesenchyme regulate the early steps of development in all ectodermal organs. Generally, the mesenchyme provides the first instructive signal, which is followed by the formation of the epithelial placode, an early signaling center. The placode buds into or out of the mesenchyme, and subsequent proliferation, cell movements, and differentiation of the epithelium and mesenchyme contribute to morphogenesis. The molecular signals regulating organogenesis, such as molecules in the FGF, TGFbeta, Wnt, and hedgehog families, regulate the development of all ectodermal appendages repeatedly during advancing morphogenesis and differentiation. In addition, signaling by ectodysplasin, a recently identified member of the TNF family, and its receptor Edar is required for ectodermal organ development across vertebrate species. Here the current knowledge on the molecular regulation of the initiation, placode formation, and morphogenesis of ectodermal organs is discussed with emphasis on feathers, hair, and teeth.

Animals↗

PubMed1998

Instructive roles of neurotrophins in synaptic plasticity.

Together, these experiments show that neurotrophins regulate neuronal function in a factor-dependent fashion, both in terms of membrane excitability and dendritic growth, and indicate that neurotrophins can play instructive roles in regulating neuronal phenotype and function. Given that neurons generally receive neurotrophic inputs from many different cellular sources, both regional and distant (e.g., via axonal and dendritic projections), instructive actions of neurotrophic factors may contribute to matching the morphology and electrical function of neurons to the neural circuits of which they are part. Moreover, during ongoing development and function of the nervous system, these same or similar neurotrophic factors may be key instructive signals in regulating synaptic plasticity of neural circuits.

Animals↗

PubMed1998

Role of reelin in the control of brain development.

Reeler is an autosomal recessive mutation in mice that results in widespread disruption of laminated regions of the brain. We isolated a gene, reelin, that is mutated in reeler mice. The protein product of reelin has features of extracellular matrix components and it is expressed in a temporal and spatial pattern during embryonic and postnatal development consistent with the phenotypic defects in reeler mice. To understand the molecular basis of the function of Reelin, we constructed a full length reelin clone and used it to direct Reelin expression. Using this clone we found that Reelin is a secreted glycoprotein and that a highly charged C-terminal region is essential for secretion. Furthermore, we demonstrated that an amino acid sequence present in the N-terminal region of Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody. CR-50 was raised against an antigen expressed in normal mouse brain that is absent in reeler mice. The interaction of CR-50 with its epitope has been shown to disrupt neuronal migration in vitro and in vivo. We used CR-50 to precipitate p385 Reelin from reticulocyte extracts programmed with reelin mRNA, from cells transfected with reelin clones and from cerebellar explants. Reelin appears to function as an instructive signal in the regulation of cell patterning during development.

Aging↗

PubMed1998

The role of the brachyury gene in heart development and left-right specification in the mouse.

The midline has a theoretical role in the development of left-right asymmetry, and this is supported by both genetic analyses and experimental manipulation of midline structures in vertebrates. The mouse brachyury (T) gene encodes a transcription factor which is expressed in the developing notochord and is required for its development. T/T mice lack a mature notochord and have a dorsalised neural tube. We have examined the hearts of T/T mice and have found consistent morphological abnormalities, resulting in ventrally displaced ventricular loops, and a 50% incidence of inverted heart situs. Three TGF-beta related genes, lefty-1, lefty-2 and nodal, are expressed asymmetrically in mouse embryos, and are implicated in the development of situs. We find that nodal, which is normally expressed around the node and in left lateral plate mesoderm in early somite embryos, is completely absent at this stage in T/T embryos. In contrast, lefty-1 and lefty-2, which are normally expressed in the left half of prospective floorplate and left lateral plate mesoderm, respectively, are both expressed in T/T embryos only in a broad patch of ventral cells in, and just rostral to, the node region. These results implicate the node as a source of instructive signals driving expression of nodal and lefty-2 in the left lateral plate mesoderm, and being required for normal looping and situs of the heart.

Animals↗

PubMed2001

Molecules involved in the formation of synaptic connections in muscle and brain.

Synapses are highly specialized structures designed to guarantee precise and efficient communication between neurons and their target cells. Molecules of the extracellular matrix have an instructive role in the formation of the neuromuscular junction, the best-characterized synapse. In this review, the molecular mechanisms underlying these instructive signals will be discussed with particular emphasis on the receptors involved. Additionally, recent evidence for the involvement of specific adhesion complexes in the formation and modulation of synapses in the central nervous system will be reviewed. Synapses are specialized junctions between neurons and their target cells where information is transferred from the pre- to the postsynaptic cell. At most vertebrate synapses, this transfer is accomplished by the release of a specific neurotransmitter from the presynaptic nerve terminal. The release of neurotransmitter is initiated by the action potential and the subsequent influx of Ca(2+) into the presynaptic nerve terminal. This results in the rapid fusion of vesicles with the nerve membrane and the release of the neurotransmitter into the synaptic cleft. The neurotransmitter then diffuses across the cleft and binds to specific postsynaptic receptors, resulting in a change in the membrane potential of the postsynaptic cell. This can result in the generation of an action potential. The high precision of synaptic transmission requires that pre- and postsynaptic structures are both highly organized and in juxtaposition to each other. In addition, alterations in synaptic transmission are the basis of learning and memory and are likely to be accompanied by the remodeling of synaptic structures (Toni et al., 1999). Thus, the study of how synapses are formed during development is also of relevance for the understanding of the cellular and molecular processes involved in learning and memory. This review focuses on the molecular mechanisms involved in the formation and the function of synapses.

Animals↗

PubMed2000

Lineage commitment in lymphopoiesis.

The mechanisms controlling the commitment of hematopoietic progenitor cells to the lymphoid lineages are still mostly unknown. Recent findings indicate that the earliest phase of B cell development may proceed in two steps. At the onset of B-lymphopoiesis, the transcription factors E2A and EBF coordinately activate the B-cell-specific gene expression program. Subsequently, Pax5 appears to repress the promiscuous transcription of lineage-inappropriate genes and thus commits progenitor cells to the B-lymphoid pathway by suppressing alternative cell fates. B-lineage commitment by Pax5 seems to occur in a stochastic manner in the bone marrow, as indicated by the random activation of only one of the two Pax5 alleles in early pro-B cells. In contrast, loss- and gain-of-function analyses have implicated the Notch1 receptor in the specification of the T cell fate, which may thus be controlled by instructive signals in the thymus.

Animals↗

PubMed1997

CD8 lineage commitment in the absence of CD8.

The absence of cytotoxic T lymphocyte activity and the failure of MHC class I-restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8alpha-deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We report that variants of the antigenic peptide that delete TCR transgenic thymocytes from CD8 wild-type but not CD8alpha-deficient mice can restore positive selection of CD8 lineage cells in the absence of CD8. The positively selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic peptide, and express CD8beta mRNA. Interestingly, there was no enhanced selection of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of CD8, provided instructive signaling for commitment to the CD8 lineage. Our results are discussed in terms of recent models of T cell lineage commitment.

Animals↗