共查询到20条相似文献,搜索用时 46 毫秒
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The myelin proteolipid protein (PLP) gene (Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.Received 4 August 2003; received after revision 17 September 2003; accepted 24 September 2003 相似文献
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Heat shock genes exhibit complex patterns of spatial and temporal regulation during embryonic development of a wide range
of organisms. Our laboratory has been involved in an analysis of heat shock gene expression in the zebrafish, a model system
which is now utilized extensively for the examination of early embryonic development of vertebrates. Members of the zebrafish
hsp47, hsp70 and hsp90 gene families have been cloned and shown to be closely related to their counterparts in higher vertebrates.
Expression of these genes has been examined using Northern blot and whole mount in situ hybridization analyses. Both the hsp47
and hsp90 genes are expressed in a highly tissue-restricted manner during normal development. The data raise a number of interesting
questions regarding the function and regulation of these heat shock genes during early zebrafish development. 相似文献
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Ouria Dkhissi-Benyahya Christine Coutanson Kenneth Knoblauch Hasna Lahouaoui Vincent Leviel Catherine Rey Mohamed Bennis Howard M. Cooper 《Cellular and molecular life sciences : CMLS》2013,70(18):3435-3447
The retinal circadian clock is crucial for optimal regulation of retinal physiology and function, yet its cellular location in mammals is still controversial. We used laser microdissection to investigate the circadian profiles and phase relations of clock gene expression and Period gene induction by light in the isolated outer (rods/cones) and inner (inner nuclear and ganglion cell layers) regions in wild-type and melanopsin-knockout (Opn 4 ?/? ) mouse retinas. In the wild-type mouse, all clock genes are rhythmically expressed in the photoreceptor layer but not in the inner retina. For clock genes that are rhythmic in both retinal compartments, the circadian profiles are out of phase. These results are consistent with the view that photoreceptors are a potential site of circadian rhythm generation. In mice lacking melanopsin, we found an unexpected loss of clock gene rhythms and of the photic induction of Per1-Per2 mRNAs only in the outer retina. Since melanopsin ganglion cells are known to provide a feed-back signalling pathway for photic information to dopaminergic cells, we further examined dopamine (DA) synthesis in Opn 4 ?/? mice. The lack of melanopsin prevented the light-dependent increase of tyrosine hydroxylase (TH) mRNA and of DA and, in constant darkness, led to comparatively high levels of both components. These results suggest that melanopsin is required for molecular clock function and DA regulation in the retina, and that Period gene induction by light is mediated by a melanopsin-dependent, DA-driven signal acting on retinal photoreceptors. 相似文献
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The central nervous system (CNS) is considered an immune-privileged organ that maintains an adaptable immune surveillance
system. Dysregulated immune function within the CNS contributes to the development of brain tumor growth, and robust immune
activation results in excessive inflammation. Human lymphocyte antigen-G (HLA-G) proteins with tolerogenic immunoreactivity
have been implicated in various pathophysiological processes including immune surveillance, governing homeostasis and immune
regulation. In this review, we describe the wealth of evidence for the involvement of HLA-G in the CNS under physiological
and pathological conditions. Further, we review regulatory functions that may be applicable as beneficial strategies in the
therapeutic manipulation of immune-mediated CNS immune responses. Additionally, we try to understand how this molecule cooperates
with other CNS-resident cells to maintain normal immune homeostasis, while still facilitating the development of the appropriate
immune responses. 相似文献
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Understanding how thousands of different neuronal types are generated in the CNS constitutes a major challenge for developmental neurobiologists and is a prerequisite before considering cell or gene therapies of nervous lesions or pathologies. During embryonic development, spinal motor neurons (MNs) segregate into distinct subpopulations that display specific characteristics and properties including molecular identity, migration pattern, allocation to specific motor columns, and innervation of defined target. Because of the facility to correlate these different characteristics, the diversification of spinal MNs has become the model of choice for studying the molecular and cellular mechanisms underlying the generation of multiple neuronal populations in the developing CNS. Therefore, how spinal motor neuron subpopulations are produced during development has been extensively studied during the last two decades. In this review article, we will provide a comprehensive overview of the genetic and molecular mechanisms that contribute to the diversification of spinal MNs. 相似文献
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Fernando de Castro Ana Bribián Mª Cristina Ortega 《Cellular and molecular life sciences : CMLS》2013,70(22):4355-4368
Oligodendrocytes are the myelin-forming cells in the central nervous system (CNS). These cells originate from oligodendrocyte precursor cells (OPCs) during development, and they migrate extensively from oligodendrogliogenic niches along the neural tube to colonise the entire CNS. Like many other such events, this migratory process is precisely regulated by a battery of positional and signalling cues that act via their corresponding receptors and that are expressed dynamically by OPCs. Here, we will review the cellular and molecular basis of this important event during embryonic and postnatal development, and we will discuss the relevance of the substantial number of OPCs existing in the adult CNS. Similarly, we will consider the behaviour of OPCs in normal and pathological conditions, especially in animal models of demyelination and of the demyelinating disease, multiple sclerosis. The spontaneous remyelination observed after damage in demyelinating pathologies has a limited effect. Understanding the cellular and molecular mechanisms underlying the biology of OPCs, particularly adult OPCs, should help in the design of neuroregenerative strategies to combat multiple sclerosis and other demyelinating diseases. 相似文献
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It has long been thought that astrocytes, like other glial cells, simply provide a support mechanism for neuronal function in the healthy and inflamed central nervous system (CNS). However, recent evidence suggests that astrocytes play an active and dual role in CNS inflammatory diseases such as multiple sclerosis (MS). Astrocytes not only have the ability to enhance immune responses and inhibit myelin repair, but they can also be protective and limit CNS inflammation while supporting oligodendrocyte and axonal regeneration. The particular impact of these cells on the pathogenesis and repair of an inflammatory demyelinating process is dependent upon a number of factors, including the stage of the disease, the type and microenvironment of the lesion, and the interactions with other cell types and factors that influence their activation. In this review, we summarize recent data supporting the idea that astrocytes play a complex role in the regulation of CNS autoimmunity. 相似文献
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The polypyrimidine tract binding protein (PTB) is a 58-kDa RNA binding protein involved in multiple aspects of mRNA metabolism
including splicing regulation, polyadenylation, 3′end formation, internal ribosomal entry site-mediated translation, RNA localization
and stability. PTB contains four RNA recognition motifs (RRMs) separated by three linkers. In this review we summarize structural
information on PTB in solution that has been gathered during the past 7 years using NMR spectroscopy and small-angle X-ray
scattering. The structures of all RRMs of PTB in their free state and in complex with short pyrimidine tracts, as well as
a structural model of PTB RRM2 in complex with a peptide, revealed unusual structural features that provided new insights
into the mechanisms of action of PTB in the different processes of RNA metabolism and in particular splicing regulation.
Received 16 August 2007; received after revision 18 September 2007; accepted 2 October 2007 相似文献
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Salminen A Ojala J Huuskonen J Kauppinen A Suuronen T Kaarniranta K 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1049-1058
Research on aging in model organisms has revealed different molecular mechanisms involved in the regulation of the lifespan.
Studies on Saccharomyces cerevisiae have highlighted the role of the Sir2 family of genes, human Sirtuin homologs, as the longevity factors. In Caenorhabditis elegans, the daf-16 gene, a mammalian homolog of FoxO genes, was shown to function as a longevity gene. A wide array of studies has
provided evidence for a role of the activation of innate immunity during aging process in mammals. This process has been called
inflamm-aging. The master regulator of innate immunity is the NF-κB system. In this review, we focus on the several interactions
of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-κB signaling pathways. We provide evidence
that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-κB signaling and simultaneously protect against inflamm-aging process.
Received 4 October 2007; received after revision 7 November 2007; accepted 9 November 2007 相似文献
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Kaia Achim Marjo Salminen Juha Partanen 《Cellular and molecular life sciences : CMLS》2014,71(8):1395-1415
Neurons using gamma-aminobutyric acid (GABA) as their neurotransmitter are the main inhibitory neurons in the mature central nervous system (CNS) and show great variation in their form and function. GABAergic neurons are produced in all of the main domains of the CNS, where they develop from discrete regions of the neuroepithelium. Here, we review the gene expression and regulatory mechanisms controlling the main steps of GABAergic neuron development: early patterning of the proliferative neuroepithelium, production of postmitotic neural precursors, establishment of their identity and migration. By comparing the molecular regulation of these events across CNS, we broadly identify three regions utilizing distinct molecular toolkits for GABAergic fate determination: telencephalon–anterior diencephalon (DLX2 type), posterior diencephalon–midbrain (GATA2 type) and hindbrain–spinal cord (PTF1A and TAL1 types). Similarities and differences in the molecular regulatory mechanisms reveal the core determinants of a GABAergic neuron as well as provide insights into generation of the vast diversity of these neurons. 相似文献