• Pharmacological inhibition of glycolysis in the presence of NGF impairs axon extension and growth cone dynamics within minutes without affecting axon maintenance. (jneurosci.org)
  • These data indicate that the glycolytic pathway is operative in distal axons and contributes to the rate of axon extension and growth cone dynamics in the presence of NGF and that, in the absence of NGF, the axonal glycolytic pathway is required for axon maintenance. (jneurosci.org)
  • However, the final link between axonal injury-induced retrograde signalling and the regulation of essential regenerative gene expression remains elusive. (nature.com)
  • In addition, we observed that extracellular signal-regulated kinase (ERK) axonal retrograde signalling is required for PCAF-dependent acetylation at these promoters and for their enhancement in gene expression. (nature.com)
  • Our results show the first evidence of immediate retrograde signalling leading to long-term epigenetic reprogramming of gene expression of select genes whose modulation leads to axonal regeneration in the hostile spinal environment. (nature.com)
  • For successful transgene expression, viruses administered into muscle must undergo a series of processes, including host cell interaction and internalization, intracellular sorting, long-range retrograde axonal transport, endosomal liberation, and nuclear import. (frontiersin.org)
  • Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway , regulate synaptic development in vertebrates and invertebrates. (sdbonline.org)
  • At the Drosophila larval neuromuscular junction (NMJ) , the retrograde BMP pathway is part of the machinery that controls NMJ expansion concurrent with larval growth. (sdbonline.org)
  • Here we show through systematic epigenetic studies that the histone acetyltransferase p300/CBP-associated factor (PCAF) promotes acetylation of histone 3 Lys 9 at the promoters of established key regeneration-associated genes following a peripheral but not a central axonal injury. (nature.com)
  • Finally, PCAF is necessary for conditioning-dependent axonal regeneration and also singularly promotes regeneration after spinal cord injury. (nature.com)
  • Thus, we find a specific epigenetic mechanism that regulates axonal regeneration of CNS axons, suggesting novel targets for clinical application. (nature.com)
  • Identification of a specific regulatory mechanism shared by several essential genes may lead to novel molecular strategies recapitulating the conditioning effect, thus non-surgically enhancing axonal regeneration in the CNS. (nature.com)
  • Finally, we established that PCAF is required for regeneration following a conditioning lesion and PCAF overexpression promotes axonal regeneration similar to that of a conditioning lesion after CNS injury in spinal ascending sensory fibres. (nature.com)
  • One possible cognate receptor for BAFF includes the Nogo receptor (NgR) and its homologs, previously established as potent inhibitors of axonal regeneration during central nervous system (CNS) injury and disease. (medsci.org)
  • Isolated Aplysia neurons have also become valuable tools for investigating the basic biology of neurite growth and regeneration. (nature.com)
  • The data reveal that the glycolytic pathway is required for normal sensory axon extension in the presence of NGF, while in the absence of NGF the glycolytic pathway is required for axon maintenance. (jneurosci.org)
  • Myosin II activity is required for axon retraction but not growth cone collapse. (biologists.com)
  • CRMP expression is highest when neurons and synaptic connections mature actively during the first postnatal week, suggesting CRMPs' role in neuronal migration, differentiation and axonal growth. (wikipedia.org)
  • The existence of mRNAs retaining both nuclear cap binding protein and EJC in the distal sites of neuronal processes suggests that some localized mRNAs have not yet undergone the "very first translation," which contribute to the spatio-temporal regulation of gene expression. (frontiersin.org)
  • Guidance cues activate signaling transduction pathways that, in turn, regulate the dynamics and organization of the neuronal cytoskeleton. (biologists.com)
  • Although much evidence supports the role of endogenous NGF in promoting neuronal survival in vivo ( Barde, 1989 ), less is known about its ability to influence axonal growth. (jneurosci.org)
  • Neuronal loss of the serine-threonine protein kinase Tao , a regulator of the Hippo signaling pathway, results in supernumerary boutons, each of which contain a normal number of active zones. (sdbonline.org)
  • Here we show that pharmacological stimulation of 5-HT7R using a highly selective agonist, LP-211, enhances neurite outgrowth in neuronal primary cultures from the cortex, hippocampus and striatal complex of embryonic mouse brain, through multiple signal transduction pathways. (cirn-na.com)
  • During neuronal development, axons navigate to their targets by sensing attractive and repulsive signals through receptors located on their growth cones [ 1 ]. (biomedcentral.com)
  • Using embryonic chicken sensory neurons, we report that glycolytic enzymes are found through the axon and the growth cone. (jneurosci.org)
  • While recent work has emphasized the importance of mitochondrial oxidative phosphorylation, the role of the glycolytic pathway in axon morphogenesis and maintenance remains minimally understood. (jneurosci.org)
  • The growth cone is the site of axon extension, and it is characterized by a complex morphology wholly dependent on the actin filaments that underlie filopodia and lamellipodia formation and dynamics ( Dent and Gertler, 2003 ). (jneurosci.org)
  • CRMPs are predominantly expressed in the nervous system during development and play important roles in axon formation from neurites and in growth cone guidance and collapse through their interactions with microtubules. (wikipedia.org)
  • Axon guidance is mediated by the effects of attractant and repellent guidance cues on the cytoskeleton of growth cones and axons. (biologists.com)
  • I investigated the roles of RhoA-kinase and myosin II in semaphorin-3A-induced growth cone collapse and axon retraction. (biologists.com)
  • Collectively, these observations suggest that guidance cues cause axon retraction through the coordinated activation of myosin II and the formation of intra-axonal F-actin bundles for myosin-II-based force generation. (biologists.com)
  • Growth cone collapse is often followed by axon retraction. (biologists.com)
  • Axon retraction induced by guidance cues is of fundamental importance during refinement of axonal projections (reviewed in Luo and O'Leary, 2005 ). (biologists.com)
  • F-actin is concentrated at the growth cone and sparse in the axon ( Letourneau, 1983 ). (biologists.com)
  • Importantly, repellent guidance cues cause growth cone collapse and depolymerize growth cone F-actin while promoting axon retraction ( Gallo and Letourneau, 2004 ). (biologists.com)
  • how can myosin II drive axon retraction if the major source of the required substratum for force generation, growth cone F-actin, has been depleted? (biologists.com)
  • Group of researchers led by Goshima found out that CRMP-2 played a role in the transduction of the extracellular Semaphorin 3A (Sema3A), an inhibitory protein for axonal guidance in chick dorsal root ganglion (DRG). (wikipedia.org)
  • I report that semaphorin 3A activates myosin II in growth cones and axons. (biologists.com)
  • Furthermore, semaphorin 3A promotes the formation of intra-axonal F-actin bundles in concert with the loss of F-actin in growth cone lamellipodia and filopodia. (biologists.com)
  • These results suggest that endogenous FGF-2 promotes cholinergic axonal sprouting in the injured adult brain. (jneurosci.org)
  • Sema 3A mediated retraction appears to be related to its binding to Npn 1 and Plxn A2 receptors, thus activating the downstream Fyn tyrosine kinase pathway that promotes the threonine-serine kinase cyclin-dependent kinase 5, CDK5, phosphorylation at the Tyr15 residue and the CDK5 processing to generate the active fragment p35. (biomedcentral.com)
  • We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
  • The aim of our study was to identify molecular changes produced by prenatal exposure to WIN 55,212-2 that might contribute to late disruption in synaptic plasticity and cognition. (researchgate.net)
  • Organisms usually contain large numbers of sphingolipid subspecies (for a pathway based compilation, see www.sphingomap.org) and knowledge about the types and amounts is imperative because they influence membrane structure, interactions with the extracellular matrix and neighboring cells, vesicular traffic and the formation of specialized structures such as phagosomes and autophagosomes, as well as participate in intracellular and extracellular signaling. (sphingolipidclub.com)
  • Here we present data indicating that when overexpressed, Sema 3A causes human neural progenitors (NP) axonal retraction and an aberrant dendritic arborization. (biomedcentral.com)
  • The impact of sphingolipids on MDR1 gene expression in cancer appears to reflect the myriad intracellular signaling pathways of ceramide and its metabolites. (sphingolipidclub.com)
  • Rescue of GAPDH using KillerRed fused to GAPDH followed by localized chromophore-assisted light inactivation of KillerRed-GAPDH in distal axons halts growth cone dynamics. (jneurosci.org)
  • In my laboratory researchers are examining the roles played by axonal cytoskeletal proteins in nervous system development, and in the etiology of Alzheimer's and other related neurodegenerative diseases. (uml.edu)
  • We examined both DNA methylation and various key histone modifications with regards to gene regulation following axonal injury. (nature.com)
  • Regulation of organ size is essential in animal development, and Hippo (Hpo) signaling is a major conserved mechanism for controlling organ growth. (sdbonline.org)
  • This study provides insights into the mechanism of Tao-1 regulation and a potential growth control function for SCHIP1 in mammals. (sdbonline.org)
  • The current proposal takes a fresh look at trying to understand how a single DNA element, the cyclic AMP-regulated enhancer (CRE), participates in the diverse regulation element in the somatostatin and PEPCK genes, the CRE has been found to contribute to the regulation of dozens of cellular, viral, and even plant genes. (grantome.com)
  • Using a high-throughput Luminex assay of NSCLC tissues, the present study identified growth associated protein 43 (GAP43), an axonal membrane protein, as an independent predictor of brain metastasis. (biomedcentral.com)
  • Axonal regenerative failure is a major cause of neurological impairment following central nervous system (CNS) but not peripheral nervous system (PNS) injury. (nature.com)
  • The regenerative response initiated following axonal injury in the peripheral nervous system (PNS) versus the central nervous system (CNS) leads to differential growth capacities and repair. (nature.com)
  • The dorsal root ganglia (DRG) sensory neurone system has a central as well as a peripheral axonal branch departing from a single cell body. (nature.com)
  • The majority of studies has investigated the function of nerve growth factor (NGF), the best-characterized member of the neurotrophin family of trophic molecules ( Korsching, 1993 ). (jneurosci.org)
  • This effect was associated with decreased activation of pathways linked to neurotrophin and glutamate receptor signaling. (researchgate.net)
  • Ephrins and Eph receptors are especially highly expressed in the embryonic nervous system, where their signalling is important for proper axonal pathfinding and to establish topographic projections [1-3]. (123dok.org)
  • Additionally, we describe how neuropathology can negatively influence these pathways, and conclude by discussing opportunities to optimize the intramuscular administration route to maximize gene delivery and thus therapeutic potential. (frontiersin.org)
  • In this context, a new molecule, B-cell activating factor (BAFF), has emerged as a positive regulator of B cell survival and differentiation functioning through various signaling pathways and potentiating the activity of various receptor complexes through pleiotropic means. (medsci.org)
  • Our research focuses on characterising the stem and progenitor cells that build the hypothalamus and characterising the molecular networks that direct hypothalamic morphogenesis, growth and differentiation. (sheffield.ac.uk)
  • Fu T, Towers M & Placzek M (2017) Fgf10(+) progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation. . (sheffield.ac.uk)
  • This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. (nih.gov)
  • Prezygotic transcripts included multiple regulators that are most likely involved in developmental processes that take place long after fertilization, such as components of ErbB, hedgehog, notch, retinoid, TGFb, VEGF and Wnt signaling pathways, as well as transcripts involved in the development of nervous system. (biomedcentral.com)
  • may provide an advantage when competing for limiting nutrients with endogenous microbial communities as well as contribute to severe disease given a rapid growth rate within sterile sites of the body. (dub-signal.com)
  • Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. (sdbonline.org)
  • We found that p300/CBP-associated factor (PCAF)-dependent acetylation of histone 3 lysine 9 (H3K9ac), paralleled by a reduction in methylation of H3K9 (H3K9me2), occurred at the promoters of select genes only after PNS axonal injury. (nature.com)
  • But can a relatively small set of amino acid changes in metabolic genes really account for such drastic growth differences? (dub-signal.com)
  • Accordingly, the neuroprotective mechanism of Rg1 is related to the activity that inhibits myosin IIA-actin interaction and the caspase-3/ROCK1/MLC signaling pathway. (ijbs.com)
  • Guidance cues can steer growth cones towards or away from the source of the cue. (biologists.com)
  • Repellent guidance cues induce growth cone collapse, characterized by the loss of protrusive lamellipodia and filopodia ( Gallo and Letourneau, 2004 ). (biologists.com)
  • Title: Could chromatic aberration allow for an alternative evolutionary pathway towards color vision? (rctn.org)
  • It is possible that the resulting adaptive mutations in the overall metabolism of USA300 directly contribute to the evolutionary success of this clone. (dub-signal.com)
  • These authors contributed equally to this manuscript. (medsci.org)
  • The authors contributed equally to this work. (ijbs.com)
  • Formation of axonal F-actin bundles was independent of myosin II, but partially required RhoA-kinase activity. (biologists.com)
  • The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. (sdbonline.org)
  • Kiyoshi Sakai and Akihito Yamamoto contributed equally to this work. (jci.org)
  • In the pancreatic acinar cell CN plays a role in mediating the action of elevated Ca 2+ to stimulate cell division, pancreatic growth and protein synthesis. (pancreapedia.org)
  • Our findings suggest that GAP43 is an independent predictor of NSCLC brain metastasis and that it may facilitate metastasis by regulating the Rac1/F-actin pathway. (biomedcentral.com)
  • It is, therefore, likely that multiple growth factors act coordinately to elicit the structural and functional changes that take place during dynamic growth processes. (jneurosci.org)
  • Considering filament polymerization requires ATP, inhibition of glycolysis results in a paradoxical increase in axonal actin filament levels. (jneurosci.org)
  • It is this inertial movement of the brain that results in traumatic diffuse axonal injury. (medscape.com)
  • Numerous clinical trials conducted in participants living with relapsing MS and PPMS have contributed to the understanding of MS pathogenesis allowing for development and management of this heterogeneous disease through targeted disease modifying therapies (DMTs) as the stochastic nature of symptoms evolve [ 4 ]. (medsci.org)
  • This study sought to determine whether the conserved Hippo pathway , critical for proportional growth in other tissues, also functions in NMJ development. (sdbonline.org)
  • Sensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. (sdbonline.org)
  • To gain insight this study quantitatively investigated synaptic growth and connectivity in the Drosophila nociceptive network during larval development. (sdbonline.org)
  • Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. (sdbonline.org)
  • In summary, the present data suggest that deficits of BDNF levels and signaling through ERK1/2 and alpha-CaMKII might contribute to cognitive and neuroplastic defects associated with prenatal exposure to cannabinoids. (researchgate.net)
  • 2007). These adapted strains exhibited major alterations in metabolic flux capacity through gluconeogenic and pyruvate catabolic pathways, yet none of these changes were because of altered gene expression. (dub-signal.com)
  • Although the mechanisms of gene activation are still unclear, ceramide's role as a messenger of cytotoxic response to chemotherapy might be linked to the MDR pathway. (sphingolipidclub.com)
  • Even within a single gene, the CRE appears to be involved in the response to multiple regulatory pathways. (grantome.com)
  • Inconsistencies have been also reported in Sema 3A knock-out (KO) mice, where the lack in Sema 3A can cause either a reduction or an increase in terminal basket cell axonal arborization [ 8 ]. (biomedcentral.com)
  • presence of DNA pathway members( DSBs) is gamma cancers of the MRN pro-B-cell, been of MRE11A, RAD50 and NBN( NBS1). (erik-mill.de)
  • The resultant cell suspension was plated in 96 well plates, HAT selected and cultured for ten 14 days to allow clonal growth applying conventional hybridoma engineering previously described. (liverxreceptor.com)
  • In Drosophila, Hpo and Warts kinases are core components of this pathway and function as tumor suppressors by inhibiting Yorkie (Yki) . (sdbonline.org)
  • Knockdown of GAPDH simplifies growth cone morphology and is rescued by shRNA-resistant GAPDH expression. (jneurosci.org)
  • Further inspection in our laboratory revealed that USA300 clones have growth advantages when metabolizing many different carbon sources (Table 1). (dub-signal.com)
  • Laboratory adaptation of Escherichia coli to growth on lactate resulted in strains that exhibited nearly twice the growth rate on lactate alone (Hua et al. (dub-signal.com)
  • The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. (cirn-na.com)
  • The primary damages are those that occur at the moment of the injury and include scalp lacerations, skull fractures, contusions and lacerations of the brain, diffuse axonal injury, and the intracranial hemorrhages. (medscape.com)