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10.1523/jneurosci.5633-07.2008 | 20,496,120 | The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated by cross-talk interactions with amyloid β peptide (Aβ), which... | 10.1038/nrn2620 | This paper showed that APOE4 and Aβ synergistically activate neurotoxic pathways that lead to neurodegeneration and cognitive deficits in mice. |
10.1523/jneurosci.4315-03.2004 | 122,994,767 | Apolipoprotein E (apoE) is found in amyloid plaques and neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains, but its role in their pathogenesis is unclear. Previously, we found C-terminal-truncated fragments of apoE in AD brains and showed that such fragments can cause neurodegeneration and can induce NFT... | 10.1038/nrn2620 | This paper demonstrated that neuronal expression of APOE4 leads to increased tau phosphorylation. |
10.1126/science.294.5545.1354 | 125,149,448 | The molecular mechanisms controlling synaptogenesis in the central nervous system (CNS) are poorly understood. Previous reports showed that a glia-derived factor strongly promotes synapse development in cultures of purified CNS neurons. Here, we identify this factor as cholesterol complexed to apolipoprotein E–containi... | 10.1038/nrn2620 | This paper showed that astrocyte-secreted cholesterol is essential for synaptogenesis. |
10.1126/science.8171342 | 109,171,354 | Apolipoprotein E4 (apoE4), one of the three common isoforms of apoE, has been implicated in Alzheimer's disease. The effects of apoE on neuronal growth were determined in cultures of dorsal root ganglion neurons. In the presence of β-migrating very low density lipoproteins (β-VLDL), apoE3 increased neurite outgrowth, w... | 10.1038/nrn2620 | References 131 and 132 described the differential effects of APOE isoforms in promoting neurite outgrowth. |
10.1126/science.1069609 | 41,750,077 | The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal g... | 10.1038/nrn3743 | References 17–19 highlight the discovery that a subset of RGCs are photoreceptors (intrinsically photosensitive) and express the photopigment melanopsin. |
10.1073/pnas.0808259105 | 85,590,074 | Decades of studies have shown that eliminating circadian rhythms of mammals does not compromise their health or longevity in the laboratory in any obvious way. These observations have raised questions about the functional significance of the mammalian circadian system, but have been difficult to address for lack of an ... | 10.1038/nrn3743 | This study shows, using an innovative light stimulation, that arrhythmicity in wild-type hamsters leads to changes in learning and memory. |
10.1073/pnas.1018375108 | 124,105,071 | Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern soci... | 10.1038/nrn3743 | A comprehensive study on the effects of the circadian clock on several aspects of physiology besides that of psychiatric disorders. |
10.1073/pnas.0609625104 | 62,076,228 | Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of ... | 10.1038/nrn3743 | A direct connection links a clock gene and psychiatric diseases. |
10.1073/pnas.1010180107 | 104,199,709 | Light therapy can be an effective treatment for mood disorders, suggesting that light is able to affect mood state in the long term. As a first step to understand this effect, we hypothesized that light might also acutely influence emotion and tested whether short exposures to light modulate emotional brain responses. ... | 10.1038/nrn3743 | A comprehensive study using different colours of light to implicate the melanopsin system in the modulation of the emotional responses in the human brain. |
10.1002/cne.20970 | 83,326,587 | Abstract A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic ... | 10.1038/nrn3743 | This study delineates the brain regions that are innervated by the ipRGCs. |
10.1242/dev.00576 | 38,563,707 | Oligodendrocytes, the myelinating cell type of the central nervous system,arise from a ventral population of precursors that also produces motoneurons. Although the mechanisms that specify motoneuron development are well described, the mechanisms that generate oligodendrocytes from the same precursor population are lar... | 10.1038/nrn1389 | These investigators found that mutations in the zebrafish Notch pathway resulted in failure to produce oligodendrocytes. They argue that Notch signalling preserves subsets of ventral spinal cord precursors during neurogenesis, acting with other temporally and spatially restricted factors to specify them for oligodendro... |
10.1101/gad.259003 | 20,410,191 | The mechanism that causes neural stem cells in the central nervous system to switch from neurogenesis to gliogenesis is poorly understood. Here we analyzed spinal cord development of mice in which the transcription factor Sox9 was specifically ablated from neural stem cells by the CRE/ loxP recombination system. These ... | 10.1038/nrn1389 | Conditional knockout of Sox9 resulted in failure to specify OLPs on schedule and proportionate increases in the numbers of motor neurons. This indicates that Sox9 is needed to promote a proglial specification programme in the pMN domain. |
10.1242/dev.128.14.2723 | 62,232,988 | Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this stu... | 10.1038/nrn1389 | This study describes the requirements for Nkx2.2 function in oligodendrocyte maturation but not the specification of OLPs. The data argue strongly against a p3 origin for OLPs in the neural tube of mice. This is consistent with expression data, which show Nkx2.2 proteins in migrating OLPs. |
10.1111/j.1601-183x.2005.00181.x | 45,535,448 | Here we present a newly developed tool for continuous recordings and analysis of novelty‐induced and baseline behaviour of mice in a home cage‐like environment. Aim of this study was to demonstrate the strength of this method by characterizing four inbred strains of mice, C57BL/6, DBA/2, C3H and 129S2/Sv, on locomotor ... | 10.1038/nrn2652 | This paper describes how home cage monitoring systems can be used to produce a detailed analysis of mouse home cage activity. |
10.1046/j.1460-9568.1999.00701.x | 58,526,772 | Abstract Attentional functioning in mice was assessed in an analogue of the five‐choice serial reaction time task in which the requirement was to detect brief visual stimuli presented across five spatial locations. Two hybrid strains of mice were assessed; F1 C57Bl/6xDBA/2 and C57Bl/6x129sv. Both strains acquired the t... | 10.1038/nrn2652 | Demonstration of the five-choice reaction time task for operant motor learning in the mouse in the nine-hole box. |
10.1073/pnas.0502205102 | 104,151,254 | There is currently no agreement as to how specific or general are the mechanisms underlying newborns' face preferences. We address this issue by manipulating the contrast polarity of schematic and naturalistic face-related images and assessing the preferences of newborns. We find that for both schematic and naturalisti... | 10.1038/nrn2353 | This elegant study on newborn babies replicated the finding that faces are recognised from birth and demonstrated that contrast polarity has a role in this ability: newborns preferentially looked at photographs and schematics of upright faces only when the pattern of contrast polarity was also face-like. |
10.1162/jocn.2006.18.6.932 | 83,170,370 | One of the least well understood regions of the human brain is rostral prefrontal cortex, approximating Brodmann's area 10. Here, we investigate the possibility that there are functional subdivisions within this region by conducting a meta-analysis of 104 functional neuroimaging studies (using positron emission tomogra... | 10.1038/nrn2353 | This meta-analysis of 104 functional neuroimaging studies provided strong evidence for the existence of distinct subregions of rostral PFC. Activations in the most rostral part of the PFC were particularly associated with multi-tasking, whereas more caudal activations were associated with mentalizing if they were media... |
10.1126/science.277.5322.105 | 29,309,046 | The pathogenic yeast Candida albicans regulates its cellular morphology in response to environmental conditions. Ellipsoidal, single cells (blastospores) predominate in rich media, whereas filaments composed of elongated cells that are attached end-to-end form in response to starvation, serum, and other conditions. The... | 10.1038/nrmicro2636 | The first identification of a protein that negatively controls hyphal growth and hypha-specific gene expression. |
10.1073/pnas.0804061106 | 62,078,146 | Candida albicans , the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments (elongated cells attached end-to-end). Because typical C. albicans infections contain a mixture of these morphologies it has, for many years, been difficult to... | 10.1038/nrmicro2636 | A desciption of UME6 , a hypha-specific gene that is required for hyphal growth. Importantly, this reference shows that overexpression of UME6 is sufficient for hyphal growth, suggesting that UME6 expression is a critical limiting step for hyphal growth. |
10.1046/j.1365-2958.2001.02459.x | 83,108,179 | The location of the septin ring in the germ tubes of Candida albicans hyphae and pseudohyphae was studied using an antibody to Saccharomyces cerevisiae Cdc11p. In pseudohyphae induced by growth at 35°C in YEPD or Lee's medium, a septin ring formed at or near (mean 1.8 µm) the neck between the mother cell and the germ t... | 10.1038/nrmicro2636 | This study shows that although pseudohyphae may superficially resemble hyphae, there are fundamental differences in the underlying cellular organization. The article describes a qualitative test to distinguish between hyphae and pseudohyphae. |
10.1091/mbc.01-03-0116 | 100,821,329 | The mechanism for apical growth during hyphal morphogenesis inCandida albicans is unknown. Studies fromSaccharomyces cerevisiae indicate that cell morphogenesis may involve cell cycle regulation by cyclin-dependent kinase. To examine whether this is the mechanism for hyphal morphogenesis, the temporal appearance of dif... | 10.1038/nrmicro2636 | A meticulous analysis that shows that cell cycle events occur with the same kinetics in yeast and hyphae, so that changes in cell cycle organization are not responsible for hyphal morphology. Furthermore, this analysis shows that germ tube evagination can occur before the start of the cell cycle, and thus a germ tube i... |
10.1242/jcs.02414 | 107,188,275 | Fungi grow with a variety of morphologies: oval yeast cells, chains of elongated cells called pseudohyphae and long, narrow, tube-like filaments called hyphae. In filamentous fungi, hyphal growth is strongly polarised to the tip and is mediated by the Spitzenkörper, which acts as a supply centre to concentrate the del... | 10.1038/nrmicro2636 | This investigation shows that hyphal growth is driven by a Spitzenkörper; therefore, the mechanism of polarized growth is different in hyphae and in yeast and pseudohyphae. The article illustrates the power of high-resolution imaging of fluorescently tagged proteins. |
10.1002/ana.410140412 | 83,025,825 | Abstract Thirty‐five patients, exclusively girls, from three countries had a uniform and striking progressive encephalopathy. After normal general and psychomotor development up to the age of 7 to 18 months, developmental stagnation occurred, followed by rapid deterioration of higher brain functions. Within one‐and‐a‐h... | 10.1038/nrneurol.2016.186 | The initial clinical description of 35 cases of Rett syndrome in the English-speaking literature. |
10.1126/science.1138389 | 41,682,339 | Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns pheno... | 10.1038/nrneurol.2016.186 | This study shows that overt neurological features seen in MeCP2-deficient mice can be substantially reversed by re-expression of the protein in adult mice. |
10.1111/dmcn.12984 | 124,831,505 | Aim Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Method Data were ascertained from hospital medical records, the Australian Rett Syndrome D... | 10.1038/nrneurol.2016.186 | Using the Australian population-based database, this study demonstrated the effects of spinal fusion to treat severe scoliosis in Rett syndrome. The findings indicated that survival was better in individuals who underwent surgery than in those who received conservative management, especially if scoliosis developed befo... |
10.1111/j.1469-8749.2010.03716.x | 103,948,710 | Aim Rett syndrome is a severe neurodevelopmental disorder that typically affects females. Little is known about the natural history and survival time of these females. Method We compared the survival of all Austrian female participants from Rett’s historical cohort (1966) with that of affected females registered in the... | 10.1038/nrneurol.2016.186 | This study compared survival in Rett's original cohort with an Australian population-based cohort in 2009, and demonstrated that survival at 25 years had increased from 21% to 71%. These findings have major implications for the clinical care of individuals with Rett syndrome into adulthood. |
10.1073/pnas.0602152103 | 61,066,226 | The enteric nervous system (ENS) is composed of neurons and glial cells, organized as interconnected ganglia within the gut wall, which controls persistalsis of the gut wall and secretions from its glands. The Ret receptor tyrosine kinase is expressed throughout enteric neurogenesis and is required for normal ENS devel... | 10.1038/nrn2137 | Expression profiling of the ENS (see also references 72 and 98) using DNA microarrays or real-time PCR allows characterization of the ENS transcriptome, identification of candidate HSCR susceptibility loci, and establishes genes of interest for functional studies. |
10.1002/dvdy.21033 | 102,941,089 | Abstract An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understa... | 10.1038/nrn2137 | A forward genetic screen in zebrafish (similar to that performed in reference 109) identified mutations affecting enteric neuron number and distribution, and characterized the effects on gut motility. Mutant fish containing fewer enteric neurons exhibit a disruption in the normal rostral to caudal contractile waves of ... |
10.1126/science.3086978 | 82,027,184 | Recent studies of animals with complex nervous systems, including humans and other primates, have improved our understanding of how the brain accomplishes learning and memory. Major themes of recent work include the locus of memory storage, the taxonomy of memory, the distinction between declarative and procedural know... | 10.1038/nrn2335 | This influential review outlines the main tenets of the Declarative Theory, and includes sections on short-term versus long-term memory, declarative versus procedural memory, and memory consolidation over time. |
10.1098/rstb.1971.0078 | 38,451,254 | It is proposed that the most important characteristic of archicortex is its ability to perform a simple kind of memorizing task. It is shown that rather general numerical constraints roughly determine the dimensions of memorizing models for the mammalian brain, and from these is derived a general model for archicortex.... | 10.1038/nrn2335 | This paper laid out the model that continues to be the dominant model of hippocampal function today (updated by references 18–22), including the ideas of memory-as-attractor-representations and pattern completion, and the relationship between rapid hippocampal learning and the slow accumulation of semantic knowledge in... |
10.1073/pnas.0610561104 | 102,994,730 | Amnesic patients have a well established deficit in remembering their past experiences. Surprisingly, however, the question as to whether such patients can imagine new experiences has not been formally addressed to our knowledge. We tested whether a group of amnesic patients with primary damage to the hippocampus bilat... | 10.1038/nrn2335 | This study presented evidence that hippocampal damage causes impairment in imagining complex visual scenes, using a task that did not require the recall of specific events. The patients' reports of the imagined scenes were particularly lacking in spatial coherence. |
10.1002/hipo.20240 | 82,144,485 | Abstract The hippocampus plays a crucial role within the neural systems for long‐term memory, but little if any role in the short‐term retention of some types of stimuli. Nonetheless, the hippocampus may be specialized for allocentric topographical processing, which impacts on short‐term memory or even perception. To i... | 10.1038/nrn2335 | This study provided evidence that the hippocampus is specifically required for the representation of topographical information in visual scenes, even over very short durations. |
10.1111/1467-9280.00288 | 102,433,316 | Eye movements were monitored to assess memory for scenes indirectly (implicitly). Two eye movement—based memory phenomena were observed: (a) the repetition effect, a decrease in sampling of previously viewed scenes compared with new scenes, reflecting memory for those scenes, and (b) the relational manipulation effect,... | 10.1038/nrn2335 | Together with reference 120, this study suggested that the hippocampus has a role in implicit or non-declarative relational memory. |
10.1073/pnas.73.5.1684 | 28,239,391 | Normal Drosophilia learn to avoid an odorant associated with electric shock. An X-linked mutant, dunce, has been isolated that fails to display this learning in spite of being able to sense the odorant and electric shock and showing essentially normal behavior in other respects. | 10.1038/nrn2098 | dunce was the first identified learning mutant. This paper contains an important discussion of the specificity of the mutant phenotype. |
10.1126/science.1089035 | 104,393,001 | We have developed a method for temporal and regional gene expression targeting (TARGET) in Drosophila and show the simultaneous spatial and temporal rescue of a memory defect. The transient expression of the rutabaga -encoded adenylyl cyclase in the mushroom bodies of the adult brain was necessary and sufficient to res... | 10.1038/nrn2098 | The description and use of TARGET: a system that permits spatial and temporal control of transgene expression based on a temperature sensitive variant of the GAL80 repressor of GAL4. Using this method, and that detailed in reference 136, the authors restrict expression of a rutabaga transgene to adulthood in rut mutant... |
10.1128/jb.173.22.7113-7125.1991 | 19,316,444 | The flagellins of Methanococcus voltae are encoded by a multigene family of four related genes (flaA, flaB1, flaB2, and flaB3). All four genes map within the same region of the genome, with the last three arranged in a direct tandem. Northern (RNA) blot and primer extension analyses of total cellular RNA indicate that ... | 10.1038/nrmicro2576 | First report showing that archaeal flagellins have class III signal peptides and are therefore structurally linked to type IV pili. |
10.1073/pnas.0809467105 | 125,231,112 | In contrast to the cell division machineries of bacteria, euryarchaea, and eukaryotes, no division components have been identified in the second main archaeal phylum, Crenarchaeota. Here, we demonstrate that a three-gene operon, cdv , in the crenarchaeon Sulfolobus acidocaldarius , forms part of a unique cell division ... | 10.1038/nrmicro2576 | References 137 and 138 demonstrate that the ESCRTIII proteins localize to the mid-cell during crenarchaeal cell division. |
10.1126/scisignal.2000628 | 80,159,208 | Attachment of SUMO lets insulin-like growth factor receptors act as transcriptional regulators in the nucleus. | 10.1038/nrn3209 | This paper describes a mechanism regulating ligand-bound IGF1 receptor as a transcriptional modulator, providing a possible mechanism for IGF1-specific actions. |
10.1126/science.275.5300.661 | 62,532,614 | A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K) triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70 S6K ). Experim... | 10.1038/nrn3209 | Seminal observations establishing IGF1–AKT signalling as a key pro-survival route in neurons. This work positioned ILPs as neurotrophic factors. |
10.1126/scisignal.2001173 | 16,816,385 | Cells lacking both insulin and IGF-1 receptors are resistant to apoptosis. | 10.1038/nrn3209 | This work describes a novel role of insulin and IGF1 receptors as ligand-independent entities in the control of cell survival. The fact that these receptors have a direct effect on apoptotic pathways provides new alternatives for the debate regarding the role of ILPs in ageing. |
10.1073/pnas.1001418107 | 35,912,192 | In phylogenetic reconstruction, two types of bacterial tyrosyl-tRNA synthetases (TyrRS) form distinct clades with many bacterial phyla represented in both clades. Very few taxa possess both forms, and maximum likelihood analysis of the distribution of TyrRS types suggests horizontal gene transfer (HGT), rather than an ... | 10.1038/nrmicro2802 | This paper highlights the challenge of distinguishing the patterns of HGT and of vertical inheritance. |
10.1073/pnas.71.3.971 | 123,533,997 | A system for genetic exchange in Rhodopseudomonas capsulata has been discovered. Each genetic marker thus far examined can be transferred, and many strains of Rps. capsulata can participate in genetic exchange. The mechanism of gene transfer seems unlike that of any previously described bacterial system, since genes ca... | 10.1038/nrmicro2802 | This paper describes the first GTA, now known as RcGTA. |
10.1073/pnas.97.2.859 | 86,518,457 | An unusual system of genetic exchange exists in the purple nonsulfur bacterium Rhodobacter capsulatus . DNA transmission is mediated by a small bacteriophage-like particle called the gene transfer agent (GTA) that transfers random 4.5-kb segments of the producing cell's genome to recipient cells, where allelic replacem... | 10.1038/nrmicro2802 | This paper describes the RcGTA gene cluster and regulatory genes in R. capsulatus |
10.1038/ismej.2008.35 | 27,022,665 | Abstract Bacteriophages are realized to be numerous and important components of oceanic food webs principally because of their lytic capabilities. The subtle changes that temperate phages impart to their hosts in the oceans are far less understood. Occurrences of lysogeny in the oceans correlate well with conditions un... | 10.1038/nrmicro2802 | This paper raises cogent questions about phage- and GTA-mediated transduction of genes in ocean waters. |
10.1126/science.1192243 | 57,167,972 | Viruslike particles enable lateral gene transfer among marine microorganisms. | 10.1038/nrmicro2802 | This article reports remarkable GTA-attributed gene transfer rates in natural environments. |
10.1128/jb.181.10.2992-3002.1999 | 81,347,806 | ABSTRACT Strain PS of Methanococcus voltae (a methanogenic, anaerobic archaebacterium) was shown to generate spontaneously 4.4-kbp chromosomal DNA fragments that are fully protected from DNase and that, upon contact with a cell, transform it genetically. This activity, here called VTA ( voltae transfer agent), affects ... | 10.1038/nrmicro2802 | This paper details the discovery of VTA, the first archaeal GTA to be found. |
10.1073/pnas.96.5.2192 | 38,419,264 | We report DNA and predicted protein sequence similarities, implying homology, among genes of double-stranded DNA (dsDNA) bacteriophages and prophages spanning a broad phylogenetic range of host bacteria. The sequence matches reported here establish genetic connections, not always direct, among the lambdoid phages of Es... | 10.1038/nrmicro2802 | A study that elegantly illustrates the movement of genes in the phage (and prophage) pan-genome. |
10.1099/mic.0.29013-0 | 36,539,315 | Natural genetic transformation can facilitate gene transfer in many genera of bacteria and requires the presence of extracellular DNA. Although cell lysis can contribute to this extracellular DNA pool, several studies have suggested that the secretion of DNA from living bacteria may also provide genetic material for tr... | 10.1038/nrmicro2802 | This investigation leads to the development of a model that rationalizes the maintenance of costly activities and may be applicable to GTA production. |
10.1126/science.273.5282.1709 | 123,364,546 | Members of a previously unidentified family of potassium channel subunits were cloned from rat and human brain. The messenger RNAs encoding these subunits were widely expressed in brain with distinct yet overlapping patterns, as well as in several peripheral tissues. Expression of the messenger RNAs in Xenopus oocytes ... | 10.1038/nrn1516 | This paper reports the cloning and initial characterization of the SK channels, and was crucial for the further development of research on these channels and the currents that they generate. |
10.1073/pnas.96.8.4662 | 60,516,860 | In hippocampal and other cortical neurons, action potentials are followed by afterhyperpolarizations (AHPs) generated by the activation of small-conductance Ca 2+ -activated K + channels (SK channels). By shaping the neuronal firing pattern, these AHPs contribute to the regulation of excitability and to the encoding fu... | 10.1038/nrn1516 | In this paper, the existence of the apamin-sensitive I AHP current in hippocampal pyramidal neurons was shown for the first time. For a long time, it had been believed that only the sI AHP was present in these neurons. |
10.1101/gad.1013302 | 81,577,617 | Organization of the inner ear into auditory and vestibular components is dependent on localized patterns of gene expression within the otic vesicle. Surrounding tissues are known to influence compartmentalization of the otic vesicle, yet the participating signals remain unclear. This study identifies Sonic hedgehog (Sh... | 10.1038/nrn1987 | Gain- and loss-of-function mouse models were used to demonstrate that sonic hedgehog signalling originating at the ventral midline of the neural tube is required to specify the ventral region of the otocyst, including the cochlea. |
10.1242/dev.01067 | 39,956,180 | Inner ear sensory organs and VIIIth cranial ganglion neurons of the auditory/vestibular pathway derive from an ectodermal placode that invaginates to form an otocyst. We show that in the mouse otocyst epithelium, Tbx1 suppresses neurogenin 1-mediated neural fate determination and is required for induction or proper pat... | 10.1038/nrn1987 | Used both mutant and knock-in models to demonstrate that Tbx1 is expressed in the prospective prosensory anlage and that it acts to inhibit cells with the otocyst from developing as SAG neuroblasts. |
10.1242/dev.126.8.1581 | 41,608,808 | Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed pr... | 10.1038/nrn1987 | This study, along with the study by Lowenheim et al . (reference 78) demonstrated that p27 kip1 regulates cell cycle withdrawal in the developing organ of Corti. |
10.1523/jneurosci.0618-06.2006 | 40,239,141 | Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically ind... | 10.1038/nrn2118 | Together with reference 35, these were the first two papers to show transcription-factor control of barrel-cortex connectivity. |
10.1126/science.1122511 | 62,030,031 | In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineuri... | 10.1038/nrn2118 | Uncovers the molecular mechanisms by which MEF2A/D regulates the numbers of excitatory synapses in cortical neurons. |
10.1002/aja.1001270402 | 20,709,728 | Abstract The small pyramidal neurons of layers II and III of the rat parietal cortex have been examined with both Golgi staining and electron microscopy. The cell body contains a large nucleus and only a thin rim of cytoplasm in which the Nissl substance is not well developed. A cap of Nissl substance occurs at the bas... | 10.1038/nrn1300 | One of the first ultrastructural descriptions of the morphological variability of dendritic spines. The authors propose the classification of spines into 'stubby', 'thin' and 'mushroom' types. |
10.1002/syn.890030312 | 81,059,003 | Abstract This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as part of the review is concerned with the morphologi... | 10.1038/nrn1300 | A thoughtful review of ultrastructural data relating to synaptogenesis. Vaughn proposes his 'synaptotropic' hypothesis, whereby dendritic filopodia capture axons and also produce dendritic branches. |
10.1242/jeb.153.1.225 | 125,244,223 | Examination of perturbations in the adult cerebellar connectivity, that follow well-defined lesions produced by gene mutations in the mouse, reveals a few of the numerous and intricate cellular interactions taking place during synaptogenesis. In weaver and in the central ectopia of reeler, Purkinje cells form innumerab... | 10.1038/nrn1300 | A review of the results from developmental studies of mouse mutants with defects in cerebellar circuitry. Sotelo proposes that the development of spines in Purkinje cells is largely independent of the axonal fibre. |
10.1002/cne.902030402 | 123,144,450 | Abstract Tissue removed from 3, 6, 9, 12, 15, and 21‐day‐old rats has been prepared for correlative light and electron microscopy to examine the maturation of cell bodies, dendrites, and axons of pyramidal neurons in layer V of rat visual cortex. As the size of the cell body increases steadily during the first 3 postna... | 10.1038/nrn1300 | An ultrastructural study of the development of dendrites in neocortex. The authors propose a model by which axons promote the maturation of axospinous synapses. |
10.1073/pnas.0500515102 | 42,624,322 | Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with ... | 10.1038/nrn3120 | This paper is one of the first reports that successfully links genetic variations of DISC1 to brain function and anatomy in human brains. |
10.1126/science.1112915 | 83,215,161 | The disrupted in schizophrenia 1 ( DISC1 ) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B ( PDE4B ) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relat... | 10.1038/nrn3120 | This was the original identification of the relationship between DISC1 and PDE4 in which DISC1 was shown to bind and regulate PDE4. Crucially, these experiments also identified two members of a family with mental illness with a translocation in PDE4B. Convergence of data re-ignited interest in PDE4 as a target for psyc... |
10.1126/science.1215704 | 29,181,748 | Translation Block MicroRNAs (miRNAs) are small, noncoding RNA genes that are found in the genomes of most eukaryotes, where they play an important role in the regulation of gene expression. Although whether gene activity is repressed by blocking translation of messenger RNA (mRNA) targets, or by promoting their deadeny... | 10.1038/nsmb.2296 | Together with reference 74, the first in vivo demonstration that miRNA-mediated translational repression precedes mRNA decay |
10.1126/science.277.5331.1511 | 45,483,916 | PSD-95 is a component of postsynaptic densities in central synapses. It contains three PDZ domains that localize N -methyl- d -aspartate receptor subunit 2 (NMDA2 receptor) and K + channels to synapses. In mouse forebrain, PSD-95 bound to the cytoplasmic COOH-termini of neuroligins, which are neuronal cell adhesion mol... | 10.1038/nrn1077 | Evidence that adhesion proteins might be involved in the molecular organization of the PSD at glutamatergic synapses. |
10.1083/jcb.101.2.683 | 58,567,079 | The distribution of receptors for a neurotransmitter was investigated cytochemically for the first time in the central nervous system, at synapses established on cells of the ventral horn of the rat cervical spinal cord. Three monoclonal antibodies (mAb's) raised against glycine receptors were used. Immunofluorescent s... | 10.1038/nrn1077 | The first morphological evidence, using immunocytochemistry and electron microscopy, of the postsynaptic accumulation of a receptor for neurotransmitters in the CNS. |
10.1073/pnas.73.12.4594 | 16,765,509 | We have made direct, quantitative measurements of the lateral motion and age-dependent distribution of acetylcholine receptors (AChR) on the surface of rat myotubes in primary culture. AChR were fluorescently marked with tetramethylrhodamine-labeled alpha-bungarotoxin and AChR lateral motion was measured by the fluores... | 10.1038/nrn1077 | The first use of FRAP to demonstrate that a membrane receptor, AChR, can be mobile or immobile in the cell plasma membrane. |
10.1523/jneurosci.03-01-00225.1983 | 32,899,208 | We have studied the lateral diffusion of acetylcholine (ACh) receptors in the extrajunctional region of developing myotomal muscle cell membrane of Xenopus tadpoles by a technique of local inactivation. The myotomal muscle cell surfaces of Xenopus tadpoles were exposed to external solution by gently removing the skin o... | 10.1038/nrn1077 | The initial proposal that acetylcholine receptors could aggregate at neuromuscular junctions by diffusing from perijunctional to junctional zones through a 'diffusion-trap' mechanism. |
10.1242/jcs.111.3.335 | 41,597,715 | The cellular and molecular mechanisms underlying the postsynaptic aggregation of ionotropic receptors in the central nervous system are not understood. The glycine receptor (GlyR) and its cytoplasmic domain-associated protein, gephyrin, are clustered at the postsynaptic membrane and constitute a good model for addressi... | 10.1038/nrn1077 | References 57 and 58 establish, using a competitive antagonist, that the activation of the glycine receptor is necessary for its postsynaptic accumulation during development. |
10.1073/pnas.72.8.3111 | 38,238,663 | Brownian motion (diffusion) of particles in membranes occurs in a highly anisotropic environment. For such particles a translational mobility (independent of velocity) can be defined if the viscosity of the liquid embedding the membrane is taken into account. The results of a model calculation are presented. They sugge... | 10.1038/nrn1077 | A theoretical calculation of the dependence of diffusion coefficients on object size in biological membranes. |
10.1111/j.1365-2958.2004.04341.x | 100,316,148 | Summary Activity of the Tat machinery for protein transport across the inner membrane of Escherichia coli and the chloroplast thylakoidal membrane requires the presence of three membrane proteins: TatA, TatB and TatC. Here, we show that the Tat machinery of the Gram‐positive bacterium Bacillus subtilis is very differen... | 10.1038/nrmicro2814 | This work shows that TatB proteins are not components of the Tat machinery in some Gram-positive bacteria. |
10.1046/j.1365-2958.1996.00114.x | 101,174,795 | The precursor polypeptides of periplasmic proteins binding seven types of redox cofactor have unusually long signal sequences bearing a consensus (S/T)‐R‐R‐x‐F‐L‐K motif immediately before the hydrophobic region. Such ‘double‐arginine’ signal sequences are not, in general, found on the precursors of other periplasmic p... | 10.1038/nrmicro2814 | This review proposes the existence of a bacterial protein transport system that translocates folded, cofactor-containing proteins using signal peptides that contain a conserved twin-arginine motif. |
10.1046/j.1365-2958.2003.03642.x | 20,692,550 | Summary A group of bacterial exported proteins are synthesized with N‐terminal signal peptides containing a SRRxFLK ‘twin‐arginine’ amino acid motif. Proteins bearing twin‐arginine signal peptides are targeted post‐translationally to the twin‐arginine translocation (Tat) system which transports folded substrates across... | 10.1038/nrmicro2814 | This study shows that the bacterial Tat pathway assembles substrate proteins containing TMHs. |
10.1073/pnas.0901566106 | 102,462,638 | The Tat system transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membrane of plant chloroplasts. In Escherichia coli substrate proteins initially bind to the integral membrane TatBC complex which then recruits the protein TatA to effect translocation. Overproduction of TatBC and the... | 10.1038/nrmicro2814 | This investigation yields the first low-resolution structures of purified TatBC with bound substrates. |
10.1083/jcb.200105149 | 41,464,338 | The thylakoid ΔpH-dependent pathway transports folded proteins with twin arginine–containing signal peptides. Identified components of the machinery include cpTatC, Hcf106, and Tha4. The reaction occurs in two steps: precursor binding to the machinery, and transport across the membrane. Here, we show that a cpTatC–Hcf1... | 10.1038/nrmicro2814 | This is the first study to show that the TatBC complex binds substrate proteins. |
10.1083/jcb.200202048 | 102,464,718 | The thylakoid ΔpH-dependent/Tat pathway is a novel system with the remarkable ability to transport tightly folded precursor proteins using a transmembrane ΔpH as the sole energy source. Three known components of the transport machinery exist in two distinct subcomplexes. A cpTatC–Hcf106 complex serves as precursor rece... | 10.1038/nrmicro2814 | This article demonstrates that thylakoid TatA interacts with the thylakoid TatBC complex only during substrate transport. |
10.1091/mbc.e08-12-1189 | 61,325,679 | The chloroplast Twin arginine translocation (Tat) pathway uses three membrane proteins and the proton gradient to transport folded proteins across sealed membranes. Precursor proteins bind to the cpTatC-Hcf106 receptor complex, triggering Tha4 assembly and protein translocation. Tha4 is required only for the translocat... | 10.1038/nrmicro2814 | References 91 and 92 use chemical crosslinking to show that TatA polymerization is induced in thylakoids by the substrate-bound TatBC complex and by the PMF. |
10.1073/pnas.0806338105 | 81,356,972 | The twin-arginine translocation (Tat) system transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membrane of plant chloroplasts. The essential components of the Tat pathway are the membrane proteins TatA, TatB, and TatC. TatA is thought to form the protein translocating element of the... | 10.1038/nrmicro2814 | This study uses in vivo imaging of fluorophore-tagged TatA to show that it forms large assemblies of variable stoichiometry in a TatBC-dependent manner. |
10.1083/jcb.200702082 | 122,654,254 | The twin-arginine translocation (Tat) pathway in Escherichia coli transports fully folded and assembled proteins across the energy-transducing periplasmic membrane. In chloroplasts, Tat transport requires energy input only from the proton motive force. To elucidate the mechanism and energetics of bacterial Tat protein ... | 10.1038/nrmicro2814 | This article demonstrates that the electrical potential component of the PMF is required for two distinct steps in Tat-mediated transport. |
10.1126/science.278.5342.1467 | 102,392,021 | The bacterial Sec and signal recognition particle ( ffh -dependent) protein translocation mechanisms are conserved between prokaryotes and higher plant chloroplasts. A third translocation mechanism in chloroplasts [the proton concentration difference (ΔpH) pathway] was previously thought to be unique. The hcf106 mutati... | 10.1038/nrmicro2814 | This article describes the identification of a protein component that is essential for protein transport by the plant Tat pathway, and the recognition that similar components are encoded in the genomes of bacteria. |
10.1073/pnas.0503558102 | 102,462,581 | The Tat system mediates Sec-independent transport of folded precursor proteins across the bacterial plasma membrane or the chloroplast thylakoid membrane. Tat transport involves distinct high-molecular-weight TatA and TatBC complexes. Here we report the 3D architecture of the TatA complex from Escherichia coli obtained... | 10.1038/nrmicro2814 | This article reports low-resolution structures of purified TatA complexes in detergent solution. |
10.1073/pnas.0937838100 | 61,325,686 | To examine the relationship between folding and export competence by the twin-arginine translocation (Tat) pathway we analyzed the subcellular localization of fusions between a set of eight putative Tat leader peptides and alkaline phosphatase in isogenic Escherichia coli strains that either allow or disfavor the forma... | 10.1038/nrmicro2814 | This study demonstrates that a non-natively folded protein cannot be transported by the Tat pathway and forms the basis for the proposal that the Tat pathway mediates folding quality control. |
10.1113/jphysiol.1973.sp010273 | 20,750,040 | 1. The after‐effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro‐electrodes in rabbits anaesthetized with urethane. 2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the den... | 10.1038/nrn2234 | The initial, now classic, description of LTP in the hippocampus. |
10.1126/science.277.5327.812 | 28,123,897 | Repeated administration of morphine sensitizes animals to the stimulant and rewarding properties of the drug. It also selectively increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area, a midbrain region implicated in morphine action. By viral-mediated gene transfer, a causal r... | 10.1038/nrn2234 | Demonstration that viral-mediated expression of GluR1 in the ventral tegmental area enhances the locomotor stimulatory and rewarding actions of morphine. |
10.1126/science.1142365 | 38,241,570 | The activation of metabotropic glutamate receptors (mGluRs) leads to long-term depression (mGluR-LTD) at many synapses of the brain. The induction of mGluR-LTD is well characterized, whereas the mechanisms underlying its expression remain largely elusive. mGluR-LTD in the ventral tegmental area (VTA) efficiently revers... | 10.1038/nrn2234 | References 81 and 82 present evidence that a novel form of mGluR-LTD reverses the cocaine-induced LTP at excitatory synapses on ventral tegmental area dopamine cells. |
10.1073/pnas.0511244103 | 124,226,607 | Psychostimulant-induced alteration of dendritic spines on dopaminoceptive neurons in nucleus accumbens (NAcc) has been hypothesized as an adaptive neuronal response that is linked to long-lasting addictive behaviors. NAcc is largely composed of two distinct subpopulations of medium-sized spiny neurons expressing high l... | 10.1038/nrn2234 | References 138–140 use BAC transgenic mice to demonstrate cell specific modifications of medium spiny neuron synapses in the dorsal and ventral striatum following in vivo manipulations. |
10.1038/ncomms13052 | 41,663,782 | Abstract DNA N 6 -methyldeoxyadenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to exist and play epigenetic roles in eukaryotic DNA. Here we report that 6mA accumulates up to ∼0.1–0.2% of total deoxyadenosine during early embryogenesis of vertebrates, but diminishes to the background leve... | 10.1038/nsmb.3412 | This work reported a significant elevation of the DNA 6mA level during early embryogenesis of vertebrates. The dynamic changes of 6mA may play critical roles in facilitating early embryo development. |
10.1126/science.1112009 | 125,253,650 | Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides eviden... | 10.1038/nrn3234 | References 2 and 3 reported data from the FANTOM3 project, which focused on characterizing the mammalian transcriptome and the organization of transcriptional and regulatory units in the genome, and identified the diversity of protein-coding and ncRNA transcripts that arise from overlapping transcription on both strand... |
10.1073/pnas.0904715106 | 41,685,378 | We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryon... | 10.1038/nrn3234 | This paper showed that a significant number of lincRNAs bind to PRC2- and CoREST-containing chromatin modifying complexes and act as guides for recruiting them to specific genomic loci. |
10.1126/science.1109020 | 41,626,285 | MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZ dicer ) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into m... | 10.1038/nrn3234 | This study was the first to establish the crucial part played by miRNAs in brain development. |
10.1261/rna.2123811 | 65,607,810 | We previously proposed that endogenous siRNAs may regulate synaptic plasticity and long-term gene expression in the mammalian brain. Here, a hippocampal-dependent task was employed in which adult mice were trained to execute a nose-poke in a port containing one of two simultaneously present odors in order to obtain a r... | 10.1038/nrn3234 | This study provides evidence for the expression of endo-siRNAs in the brain and for their roles in mediating learning and memory. |
10.1523/jneurosci.4163-07.2007 | 62,214,926 | Does the parietal lobe have a critical role in memory? The neuroimaging literature indicates that it has an important role, especially in episodic memory. However, the neuropsychological literature suggests that its role is more limited to attentional, spatial, or imagery aspects of memory. Here, we present data to adj... | 10.1038/nrn2459 | This study reported the first evidence of significant deficits in episodic-memory retrieval following parietal lesions. Consistent with the AtoM model, patients with bilateral ventral parietal lesions showed a deficit in spontaneously reporting details in their autobiographical memories but could provide these details ... |
10.1111/j.1460-9568.2006.04600.x | 122,954,866 | Summary Neuroimaging findings, including repetitive transcranial magnetic stimulation (rTMS) interference, point to an engagement of prefrontal cortex (PFC) in learning and memory. Whether parietal cortex (PC) activity is causally linked to successful episodic encoding and retrieval is still uncertain. We compared the ... | 10.1038/nrn2459 | This study did not find a significant effect of TMS stimulation on episodic-retrieval performance. |
10.1073/pnas.1121568109 | 107,322,421 | Dysregulation of the transcriptional repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor is important in a broad range of diseases, including cancer, diabetes, and heart disease. The role of REST-dependent epigenetic modifications in neurodegeneration is less clear. Here, we sho... | 10.1038/nrn.2017.46 | This is the first paper to show that REST assembles with co-repressors at the promoters of transcriptionally responsive target genes and orchestrates epigenetic remodelling. |
10.1073/pnas.0611704104 | 100,806,071 | Transient global ischemia is a neuronal insult that induces delayed, selective death of hippocampal CA1 pyramidal neurons. A mechanism underlying ischemia-induced cell death is activation of the gene silencing transcription factor REST (repressor element-1 silencing transcription factor)/NRSF (neuron-restrictive silenc... | 10.1038/nrn.2017.46 | This is the first paper to show the dysregulation of REST and REST-dependent epigenetic remodelling in a clinically relevant model of ischaemic stroke. |
10.1126/scisignal.2000502 | 101,033,942 | Polycomb group proteins protect neurons from injury through a mechanism involving decreased potassium channel function. | 10.1038/nrn.2017.46 | This is the first paper to show that Polycomb proteins are activated in postmitotic vertebrate neurons and are crucial for ischaemic tolerance. |
10.1073/pnas.96.1.179 | 125,064,234 | The effect of expressing human huntingtin fragments containing polyglutamine (polyQ) tracts of varying lengths was assessed in Caenorhabditis elegans ASH sensory neurons in young and old animals. Expression of a huntingtin fragment containing a polyQ tract of 150 residues (Htn-Q150) led to progressive ASH neurodegenera... | 10.1038/nrn3570 | This article demonstrates that transgenic expression of the N-terminal fragment of mHTT in C. elegans , which lacks a HTT orthologue, is sufficient to cause age-dependent neuronal dysfunction and, on a sensitized background, degeneration. |
10.1523/jneurosci.4367-07.2008 | 81,920,661 | The function of a complex nervous system depends on an intricate interplay between neuronal and glial cell types. One of the many functions of glial cells is to provide an efficient insulation of the nervous system and thereby allowing a fine tuned homeostasis of ions and other small molecules. Here, we present a detai... | 10.1038/nrn2720 | References 27 and 28 present a thorough clonal analysis of D. melanogaster glial cells during blood–brain barrier development and adult neurogenesis and demonstrate the morphologies of individual glial cells. |
10.1523/jneurosci.3583-07.2007 | 82,396,000 | Any complex nervous system is made out of two major cell types, neurons and glial cells. A hallmark of glial cells is their pronounced ability to migrate. En route to their final destinations, glial cells are generally guided by neuronal signals. Here we show that in the developing visual system of Drosophila glial cel... | 10.1038/nrn2720 | The authors identify the different glial cells of the eye imaginal disc and describe the carpet glia. Ablation experiments clarify the function of the carpet cells during the coordination of the migration of glial cells onto the eye disc. |
10.1242/dev.01398 | 38,536,830 | Migration and proliferation have been mostly explored in culture systems or fixed preparations. We present a simple genetic model, the chains of glia moving along fly wing nerves, to follow such dynamic processes by time-lapse in the whole animal. We show that glia undergo extensive cytoskeleton and mitotic apparatus r... | 10.1038/nrn2720 | Introduces the peripheral nerve and its attached glial cells as a model to follow the migration of glial chains in vivo in the intact animal. Using the MARCM (mosaic analysis with a repressible cell marker) technique, the authors reach a single-cell resolution and define the role of neuronal–glial and glial–glial inter... |
10.1523/jneurosci.1361-08.2008 | 81,795,154 | The migration of glial chains along the nerve entails directional and coordinated movement. Despite its importance in the formation of the nervous system, this process remains poorly understood, because of the difficulty of manipulating identified cells. Using confocal time-lapse and cell ablation in the whole animal, ... | 10.1038/nrn2720 | Cell ablation experiments and in vivo imaging demonstrate that tip cells guide glial cell chain migration in developing wing nerves. The tip cells generate long cell processes that influence the migration of follower cells. |
10.1126/science.1143708 | 18,987,224 | We sequenced and annotated the genome of the filamentous fungus Fusarium graminearum , a major pathogen of cultivated cereals. Very few repetitive sequences were detected, and the process of repeat-induced point mutation, in which duplicated sequences are subject to extensive mutation, may partially account for the red... | 10.1038/nrmicro2790 | The first comparative genomics study of a filamentous plant pathogen based on two isolates. It highlighted regions of high diversity enriched in infection-related genes, and proposed that these regions contribute to adaptation to changing environment and hosts. |
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