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https://www.readbyqxmd.com/read/29141180/motor-neuron-migration-and-positioning-mechanisms-new-roles-for-guidance-cues
#1
REVIEW
Minkyung Kim, Brielle Bjorke, Grant S Mastick
Motor neurons differentiate from progenitor cells and cluster as motor nuclei, settling next to the floor plate in the brain stem and spinal cord. Although precise positioning of motor neurons is critical for their functional input and output, the molecular mechanisms that guide motor neurons to their proper positions remain poorly understood. Here, we review recent evidence of motor neuron positioning mechanisms, highlighting situations in which motor neuron cell bodies can migrate, and experiments that show that their migration is regulated by axon guidance cues...
November 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29137400/downregulation-of-the-sonic-hedgehog-gli-pathway-transcriptional-target-neogenin-1-is-associated-with-basal-cell-carcinoma-aggressiveness
#2
Bárbara S Casas, Christelle Adolphe, Pablo Lois, Nelson Navarrete, Natalia Solís, Eva Bustamante, Patricio Gac, Patricio Cabané, Ivan Gallegos, Brandon J Wainwright, Verónica Palma
Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29121420/obesity-during-pregnancy-in-the-mouse-alters-the-netrin-1-responsiveness-of-fetal-arcuate-nucleus-npy-neurons
#3
Tessa R Sanders, Kelly A Glendining, Christine L Jasoni
When individuals undergo gestation in an obese dam, they are at increased risk for impairments in the brain's ability to regulate body weight. In rodents, gestation in an obese dam leads to a number of changes to the development of the hypothalamic neurons that regulate body weight, including reduced neuronal connectivity at birth. Here, we sought to gain a clearer picture of how this neural circuitry develops normally, and to explore the mechanism underpinning the deficiency in connectivity seen in fetuses developing in obese dams...
November 9, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29092889/a-statistically-oriented-asymmetric-localization-soal-model-for-neuronal-outgrowth-patterning-by-caenorhabditis-elegans-unc-5-unc5-and-unc-40-dcc-netrin-receptors
#4
Gerard Limerick, Xia Tang, Won Suk Lee, Ahmed Mohamed, Aseel Al-Aamiri, William G Wadsworth
Neurons extend processes that vary in number, length, and direction of outgrowth. Extracellular cues help determine outgrowth patterns. In Caenorhabditis elegans, neurons respond to the extracellular UNC-6 (netrin) cue via UNC-40 (DCC) and UNC-5 (UNC5) receptors. Previously we presented evidence that UNC-40 asymmetric localization at the plasma membrane is self-organizing and that UNC-40 can localize and mediate outgrowth at randomly selected sites. Here we provide further evidence for a statistically oriented asymmetric localization (SOAL) model in which UNC-5 receptor activity affects patterns of axon outgrowth by regulating UNC-40 asymmetric localization...
November 1, 2017: Genetics
https://www.readbyqxmd.com/read/29068161/dcc-mutation-update-congenital-mirror-movements-isolated-agenesis-of-the-corpus-callosum-and-developmental-split-brain-syndrome
#5
Ashley Pl Marsh, Timothy J Edwards, Charles Galea, Helen M Cooper, Elizabeth C Engle, Saumya S Jamuar, Aurélie Méneret, Marie-Laure Moutard, Caroline Nava, Agnès Rastetter, Gail Robinson, Guy Rouleau, Emmanuel Roze, Megan Spencer-Smith, Oriane Trouillard, Thierry Billette de Villemeur, Christopher A Walsh, Timothy W Yu, Delphine Heron, Elliott H Sherr, Linda J Richards, Christel Depienne, Richard J Leventer, Paul J Lockhart
The deleted in colorectal cancer (DCC) gene encodes the netrin-1 receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum, or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome...
October 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/29059224/netrin-1-is-a-novel-regulator-of-vascular-endothelial-function-in-diabetes
#6
Haroldo A Toque, Aracely Fernandez-Flores, Riyaz Mohamed, Ruth B Caldwell, Ganesan Ramesh, R William Caldwell
BACKGROUND: Netrin-1, a secreted laminin-like protein identified as an axon guidance molecule, has been shown to be of critical importance in the cardiovascular system. Recent studies have revealed pro-angiogenic, anti-apoptotic and anti-inflammatory properties of netrin-1 as well as cardioprotective actions against myocardial injury in diabetic mice. AIM: To examine the role of netrin-1 in diabetes-and high glucose (HG)-induced vascular endothelial dysfunction (VED) using netrin-1 transgenic mice (Tg3) and cultured bovine aortic endothelial cells (BAEC)...
2017: PloS One
https://www.readbyqxmd.com/read/29041904/shift-in-the-function-of-netrin-1-from-axon-outgrowth-to-axon-branching-in-developing-cerebral-cortical-neurons
#7
Hideko Matsumoto, Masabumi Nagashima
BACKGROUND: Netrin-1, a multifunctional axon guidance cue, elicits axon outgrowth via one of its receptors deleted in colorectal cancer (DCC) in several types of neurons, including cerebral cortical neurons of embryonic mice. However, we and others have observed de novo formation of axon branches without axon outgrowth induced by netrin-1 in cortical culture of neonatal hamsters. These previous reports suggested the possibility that netrin-1 function might alter during development, which we here investigated using dissociated culture prepared from cerebral cortices of embryonic mice...
October 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29032842/making-dopamine-connections-in-adolescence
#8
REVIEW
Daniel Hoops, Cecilia Flores
A dramatic maturational process ongoing in adolescence is prefrontal cortex development, including its dopamine innervation. Dopamine axons grow from the striatum to the prefrontal cortex, the only known case of long-distance axon growth during adolescence. This is coordinated by the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer), which in turn controls the intrinsic development of the prefrontal cortex itself. Stimulant drugs in adolescence alter DCC in dopamine neurons and, in turn prefrontal cortex maturation, impacting cognitive abilities...
October 9, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/29017609/effects-of-intra-arterial-transplantation-of-adipose-derived-stem-cells-on-the-expression-of-netrin-1-and-its-receptor-dcc-in-the-peri-infarct-cortex-after-experimental-stroke
#9
Huan Huang, Fan Lin, Jingjing Jiang, Yan Chen, Ainong Mei, Pengli Zhu
BACKGROUND: Stem cell transplantation has been documented to promote functional recovery in animal models of stroke; however, the underlying mechanisms are not yet fully understood. As netrin-1 and its receptor deleted in colorectal cancer (DCC) are important regulators in neuronal and vascular activities, the present study attempted to explore whether netrin-1 and DCC are involved in the neuroprotection of stem cell-based therapies in a rat ischemic stroke model. METHODS: Adult male Sprague-Dawley rats were subjected to a transient middle cerebral artery occlusion (MCAO) and subsequently received an intra-arterial injection of 2 × 10(6) PKH26-labeled adipose-derived stem cells (ADSCs) or saline 24 h later...
October 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28993416/regulation-of-axon-guidance-by-the-wnt-receptor-ror-cam-1-in-the-pvt-guidepost-cell-in%C3%A2-caenorhabditis-elegans
#10
Jason Chien, Ranjan Devkota, Nebeyu Yosef, Catarina Mörck
The Caenorhabditis elegans ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN-2 and EGL-20 or loss of the Wnt receptor CAM-1 caused more than 70 % of PVP and PVQ axons to inappropriately cross over from the left side to the right side...
October 9, 2017: Genetics
https://www.readbyqxmd.com/read/28986144/motor-axons-are-guided-to-exit-points-in-the-spinal-cord-by-slit-and-netrin-signals
#11
Minkyung Kim, Tatiana M Fontelonga, Clare H Lee, Sarah J Barnum, Grant S Mastick
In the spinal cord, motor axons project out the neural tube at specific exit points, then bundle together to project toward target muscles. The molecular signals that guide motor axons to and out of their exit points remain undefined. Since motor axons and their exit points are located near the floor plate, guidance signals produced by the floor plate and adjacent ventral tissues could influence motor axons as they project toward and out of exit points. The secreted Slit proteins are major floor plate repellents, and motor neurons express two Slit receptors, Robo1 and Robo2...
October 3, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28945198/mutations-in-the-netrin-1-gene-cause-congenital-mirror-movements
#12
Aurélie Méneret, Elizabeth A Franz, Oriane Trouillard, Thomas C Oliver, Yvrick Zagar, Stephen P Robertson, Quentin Welniarz, R J MacKinlay Gardner, Cécile Gallea, Myriam Srour, Christel Depienne, Christine L Jasoni, Caroline Dubacq, Florence Riant, Jean-Charles Lamy, Marie-Pierre Morel, Raphael Guérois, Jessica Andreani, Coralie Fouquet, Mohamed Doulazmi, Marie Vidailhet, Guy A Rouleau, Alexis Brice, Alain Chédotal, Isabelle Dusart, Emmanuel Roze, David Markie
Netrin-1 is a secreted protein that was first identified 20 years ago as an axon guidance molecule that regulates midline crossing in the CNS. It plays critical roles in various tissues throughout development and is implicated in tumorigenesis and inflammation in adulthood. Despite extensive studies, no inherited human disease has been directly associated with mutations in NTN1, the gene coding for netrin-1. Here, we have identified 3 mutations in exon 7 of NTN1 in 2 unrelated families and 1 sporadic case with isolated congenital mirror movements (CMM), a disorder characterized by involuntary movements of one hand that mirror intentional movements of the opposite hand...
September 25, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28931893/netrin-1-derived-from-the-ventricular-zone-but-not-the-floor-plate-directs-hindbrain-commissural-axons-to-the-ventral-midline
#13
Kenta Yamauchi, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Heiko Lickert, Takahiko Kawasaki, Fujio Murakami, Tatsumi Hirata
Netrin-1 (Ntn1) emanating from the ventral midline has been thought to act as a long-range diffusible chemoattractant for commissural axons (CAs). However, CAs still grow towards the midline in the absence of the floor plate (FP), a glial structure occupying the midline. Here, using genetically loss-of-function approaches in mice, we show that Ntn1 derived from the ventricular zone (VZ), but not the FP, is crucial for CA guidance in the mouse hindbrain. During the period of CA growth, Ntn1 is expressed in the ventral two-thirds of the VZ, in addition to the FP...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931811/distal-axotomy-enhances-retrograde-presynaptic-excitability-onto-injured-pyramidal-neurons-via-trans-synaptic-signaling
#14
Tharkika Nagendran, Rylan S Larsen, Rebecca L Bigler, Shawn B Frost, Benjamin D Philpot, Randolph J Nudo, Anne Marion Taylor
Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28918114/netrins-semaphorins-novel-regulators-of-the-immune-response
#15
REVIEW
Jordyn Feinstein, Bhama Ramkhelawon
Netrins and semaphorins, members of the neuronal guidance cue family, exhibit a rich biology with significant roles that extend beyond chemotactic guidance of the axons to build the neuronal patterns of the body. Screening of adult tissues and specific cellular subsets have illuminated that these proteins are also abundantly expressed under both steady state and pathological scenarios. This observation suggests that, in addition to their role in the development of the axonal tree, these proteins possess additional novel functions in adult physiopathology...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28882944/netrin-4-promotes-differentiation-and-migration-of-osteoblasts
#16
Yuichiro Enoki, Tsuyoshi Sato, Shoichiro Kokabu, Naoki Hayashi, Takanori Iwata, Masayuki Yamato, Michihiko Usui, Masahito Matsumoto, Taketo Tomoda, Wataru Ariyoshi, Tatsuji Nishihara, Tetsuya Yoda
BACKGROUND/AIM: While netrin-4 plays a vital role in the vascular system, the role of netrin-1 in osteoblast differentiation is not well understood. In this study we explored whether netrin-4 has functional roles in osteoblasts. MATERIALS AND METHODS: Quantitative reverse-transcriptase polymerase chain reaction (PCR), RNA interference, the generation of plasmids, transfections, measurement of alkaline phosphatase activity, a mineralization assay, a migration assay and a cell proliferation assay were performed...
September 2017: In Vivo
https://www.readbyqxmd.com/read/28881639/netrin-1-promotes-gastric-cancer-cell-proliferation-and-invasion-via-the-receptor-neogenin-through-pi3k-akt-signaling-pathway
#17
Kai Yin, Linjun Wang, Xuan Zhang, Zhongyuan He, Yiwen Xia, Jianghao Xu, Song Wei, Bowen Li, Zheng Li, Guangli Sun, Qing Li, Hao Xu, Zekuan Xu
Netrin-1 is a laminin-related protein found to promote proliferation and invasion in multiple types of cancers. Recent studies have identified the function role of netrin-1 in several cancers; however, the influence of netrin-1 in human gastric cancer(GC) remains largely unknown. In this study, we found netrin-1 was upregulated in human GC tissues, where its expression correlated inversely with cancer stage and lymph node metastasis. We detected netrin-1 and its receptor knockdown significantly suppressed GC cells proliferation and invasion, while overexpression netrin-1 reversed these effects...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28859089/flavin-monooxygenases-regulate-caenorhabditis-elegans-axon-guidance-and-growth-cone-protrusion-with-unc-6-netrin-signaling-and-rac-gtpases
#18
Mahekta R Gujar, Aubrie M Stricker, Erik A Lundquist
The guidance cue UNC-6/Netrin regulates both attractive and repulsive axon guidance. Our previous work showed that in C. elegans, the attractive UNC-6/Netrin receptor UNC-40/DCC stimulates growth cone protrusion, and that the repulsive receptor, an UNC-5:UNC-40 heterodimer, inhibits growth cone protrusion. We have also shown that inhibition of growth cone protrusion downstream of the UNC-5:UNC-40 repulsive receptor involves Rac GTPases, the Rac GTP exchange factor UNC-73/Trio, and the cytoskeletal regulator UNC-33/CRMP, which mediates Semaphorin-induced growth cone collapse in other systems...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28856010/serum-netrin-1-in-relation-to-gadolinium-enhanced-magnetic-resonance-imaging-in-early-multiple-sclerosis
#19
M M Voortman, T Pekar, D Bachmayer, J-J Archelos, T Stojakovic, H Scharnagl, S Ropele, A Pichler, C Enzinger, S Fuchs, F Fazekas, T Seifert-Held, M Khalil
BACKGROUND: Netrin-1, a secreted laminin-related protein, is known to regulate not only axonal guidance and neuronal cell migration, but also blood-brain barrier integrity and inflammation. Two preliminary studies reported altered serum netrin-1 levels in multiple sclerosis; however, associations with longitudinal clinical and magnetic resonance imaging activity have not been investigated. OBJECTIVES: We aimed to assess serum netrin-1 in multiple sclerosis and controls with respect to disease activity and its temporal dynamics...
July 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28851705/distinct-functions-for-netrin-1-in-chicken-and-murine-semicircular-canal-morphogenesis
#20
Allison M Nishitani, Sho Ohta, Andrea R Yung, Tony Del Rio, Michael I Gordon, Victoria E Abraira, Evelyn C Avilés, Gary C Schoenwolf, Donna M Fekete, Lisa V Goodrich
The vestibular system of the inner ear detects head position using three orthogonally oriented semicircular canals; even slight changes in their shape and orientation can cause debilitating behavioral defects. During development, the canals are sculpted from pouches that protrude from the otic vesicle, the embryonic anlage of the inner ear. In the center of each pouch, a fusion plate forms where cells lose their epithelial morphology and the basement membrane breaks down. Cells in the fusing epithelia intercalate and are removed, creating a canal...
September 15, 2017: Development
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