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Gilles Maussion, Cristiana Cruceanu, Jill A Rosenfeld, Scott C Bell, Fabrice Jollant, Jin Szatkiewicz, Ryan L Collins, Carrie Hanscom, Ilaria Kolobova, Nicolas Menjot de Champfleur, Ian Blumenthal, Colby Chiang, Vanessa Ota, Christina Hultman, Colm O'Dushlaine, Steve McCarroll, Martin Alda, Sebastien Jacquemont, Zehra Ordulu, Christian R Marshall, Melissa T Carter, Lisa G Shaffer, Pamela Sklar, Santhosh Girirajan, Cynthia C Morton, James F Gusella, Gustavo Turecki, Dimitri J Stavropoulos, Patrick F Sullivan, Stephen W Scherer, Michael E Talkowski, Carl Ernst
We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11...
October 19, 2016: American Journal of Medical Genetics. Part A
Haiyan Lu, Xiaoyan Song, Feng Wang, Guodong Wang, Yuncheng Wu, Qiaoshu Wang, Yongting Wang, Guo-Yuan Yang, Zhijun Zhang
Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent 60 min of middle cerebral artery (MCA) occlusion 1 week after injection...
2016: Frontiers in Cellular Neuroscience
Orkun Akin, S Lawrence Zipursky
Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it...
October 15, 2016: ELife
Tripti Gupta, Arun Kumar, Cattenoz Pierre, K VijayRaghavan, Angela Giangrande
Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules involved in cell interaction control collective migration, but what their precise role is and how is their expression finely tuned to orchestrate the different steps of the process is poorly understood. Here we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the Drosophila wing. Frazzled expression is induced by the Glide/Gcm transcription factor in a dose dependent manner...
October 14, 2016: ELife
Karen Stanic, Natalia Saldivia, Benjamín Förstera, Marcela Torrejón, Hernán Montecinos, Teresa Caprile
Extracellular matrix (ECM) molecules are pivotal for central nervous system (CNS) development, facilitating cell migration, axonal growth, myelination, dendritic spine formation, and synaptic plasticity, among other processes. During axon guidance, the ECM not only acts as a permissive or non-permissive substrate for navigating axons, but also modulates the effects of classical guidance cues, such as netrin or Eph/ephrin family members. Despite being highly important, little is known about the expression of ECM molecules during CNS development...
2016: Frontiers in Neuroanatomy
Kadri Murat Gurses, Fusun Ozmen, Duygu Kocyigit, Nilgun Yersal, Elif Bilgic, Erkan Kaya, Cagla Zubeyde Kopru, Tolga Soyal, Suat Doganci, Lale Tokgozoglu, Petek Korkusuz
BACKGROUND: Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated. METHODS: Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1, Unc5b, and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery...
October 7, 2016: Journal of Cardiology
Kenta Maruyama, Takahiko Kawasaki, Masahide Hamaguchi, Motomu Hashimoto, Moritoshi Furu, Hiromu Ito, Takao Fujii, Naoki Takemura, Thangaraj Karuppuchamy, Takeshi Kondo, Takumi Kawasaki, Masahiro Fukasaka, Takuma Misawa, Tatsuya Saitoh, Yutaka Suzuki, Mikaël M Martino, Yutaro Kumagai, Shizuo Akira
Netrin 1 was initially identified as an axon guidance factor and recent reports indicate that it inhibits chemokine-directed monocyte migration. Despite its importance as a neuroimmune guidance cue, the role of netrin 1 in osteoclasts is largely unknown. Here we detected high netrin 1 levels in the synovial fluid of rheumatoid arthritis patients. Netrin 1 is potently expressed in osteoblasts and synovial fibroblasts, and IL17 robustly enhances netrin 1 expression in these cells. The binding of netrin 1 to its receptor UNC5b on osteoclasts resulted in activation of SHP1, which inhibited VAV3 phosphorylation and RAC1 activation...
September 28, 2016: Journal of Biological Chemistry
Tanwarat Sanvoranart, Aungkura Supokawej, Pakpoom Kheolamai, Yaowalak U-Pratya, Niphon Poungvarin, Sith Sathornsumetee, Surapol Issaragrisil
Glioblastoma (GBM) is an aggressive malignant brain tumor that still lacks effective therapy. Glioblastoma stem cells (GBM-SCs) were identified to contribute to aggressive phenotypes and poor clinical outcomes for GBM. Netrin-1, an axon guidance molecule, has been found in several tumors in adults. However, the role of Netrin-1 in GBM-SCs remains largely unknown. In this study, CD133-positive U251 GBM cells were used as a putative GBM-SC population to identify the functions of Netrin-1. Using lentiviral transduction, Netrin-1 miR RNAi vectors were transduced into CD133-positive U251 cells...
September 20, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Joanna M Dragich, Takaaki Kuwajima, Megumi Hirose-Ikeda, Michael S Yoon, Evelien Eenjes, Joan R Bosco, Leora M Fox, Alf H Lystad, Tinmarla F Oo, Olga Yarygina, Tomohiro Mita, Satoshi Waguri, Yoshinobu Ichimura, Masaaki Komatsu, Anne Simonsen, Robert E Burke, Carol A Mason, Ai Yamamoto
The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression...
2016: ELife
Jayne Aiken, Georgia Buscaglia
No abstract text is available yet for this article.
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Qanber Raza, J Roger Jacobs
Collective cell migration is the coordinated movement of cells, which organize tissues during morphogenesis, repair and some cancers. The motile cell membrane of the advancing front in collective cell migration is termed the Leading Edge. The embryonic development of the vertebrate and Drosophila hearts are both characterized by the coordinated medial migration of a bilateral cluster of mesodermal cells. In Drosophila, the cardioblasts form cohesive bilateral rows that migrate collectively as a unit towards the dorsal midline to form the dorsal vessel...
September 9, 2016: Developmental Biology
Elena Seiradake, E Yvonne Jones, Rüdiger Klein
Axon guidance relies on a combinatorial code of receptor and ligand interactions that direct adhesive/attractive and repulsive cellular responses. Recent structural data have revealed many of the molecular mechanisms that govern these interactions and enabled the design of sophisticated mutant tools to dissect their biological functions. Here, we discuss the structure/function relationships of four major classes of guidance cues (ephrins, semaphorins, slits, netrins) and examples of morphogens (Wnt, Shh) and of cell adhesion molecules (FLRT)...
October 6, 2016: Annual Review of Cell and Developmental Biology
Xiaosheng Yang, Shiting Li, Jun Zhong, Wenchuan Zhang, Xuming Hua, Bin Li, Hui Sun
Crosstalk between the nervous and vascular systems is important during development and in response to injury, and the laminin-like axonal guidance protein netrin-1 has been studied for its involvement in angiogenesis and vascular remodelling. In this study, we examined the role of netrin-1 in angiogenesis and explored the underlying mechanisms. The effect of netrin-1 on brain tissues and endothelial cells was examined by immunohistochemistry and western blotting in a middle cerebral artery occlusion model and in human umbilical vein endothelial cells...
August 25, 2016: Journal of Cellular and Molecular Medicine
Shan Gao, Xiuyuan Zhang, Yibo Qin, Shixin Xu, Ju Zhang, Zhihong Wang, Weiwei Wang, Deling Kong, Chen Li
Netrin-1 is typically known as a neural guidance cue, which has been implicated in pancreas development. Since regenerative, angiogenic and anti-inflammatory properties of Netrin-1 have been reported in multiple tissues, we have investigated the potential role of Netrin-1 in the endocrine islet and its implication in mice with high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Effects of exogenous Netrin-1 on β-cell [Ca(2+)]i, cyclic AMP (cAMP) and insulin production were assessed in vitro The long-term impact of Netrin-1 treatment was then evaluated in HFD/STZ-induced diabetic mice by subcutaneous implantation of osmotic minipumps which release Netrin-1 in a sustained manner for 4 weeks...
November 1, 2016: Clinical Science (1979-)
Lewis Taylor, Maximillian Hugo Brodermann, David McCaffary, Asif Jilani Iqbal, David R Greaves
Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies...
2016: PloS One
Aránzazu Mediero, Tuere Wilder, Bhama Ramkhelawon, Kathryn J Moore, Bruce N Cronstein
Rheumatoid arthritis is an autoimmune disease that is characterized by chronic inflammation and destruction of joints. Netrin-1, a chemorepulsant, laminin-like matrix protein, promotes inflammation by preventing macrophage egress from inflamed sites and is required for osteoclast differentiation. We asked whether blockade of Netrin-1 or its receptors [Unc5b and DCC (deleted in colorectal carcinoma)] may be useful therapeutic targets for treatment of inflammatory arthritis. Arthritis was induced in 8-wk-old C57Bl/6 mice by intraperitoneal injection of K/BxN serum...
August 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hongbin Chen, Wei Lin, Yixian Zhang, Longzai Lin, Jianhao Chen, Yongping Zeng, Mouwei Zheng, Zezhong Zhuang, Houwei Du, Ronghua Chen, Nan Liu
As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury...
2016: Scientific Reports
Carlos A Díaz-Balzac, Maisha Rahman, María I Lázaro-Peña, Lourdes A Martin Hernandez, Yehuda Salzberg, Cristina Aguirre-Chen, Zaven Kaprielian, Hannes E Bülow
Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1-3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin-SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the leucine-rich transmembrane receptor DMA-1/LRR-TM expressed on PVD neurons [8, 9]...
September 12, 2016: Current Biology: CB
Zhankai Tang, Caiming Xu, Guixin Zhang, Hailong Chen
Neuronal guidance factor Netrin-1 has been known to be involved in nervous system development by controlling neuronal migration through both chemoattractive and chemo-repulsive signaling by binding different receptors. Netrin-1 has been shown to play a positively regulatory role during inflammatory process recently. Since the chemorepulsive receptors were found in leukocytes, it is suggest that Netrin-1 played a protective role in tissue through inhibiting leukocyte trafficking and accumulating during inflammatory process in researches...
August 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Leo Boneschansker, Hironao Nakayama, Michele Eisenga, Johannes Wedel, Michael Klagsbrun, Daniel Irimia, David M Briscoe
Netrin-1 is a neuronal guidance cue that regulates cellular activation, migration, and cytoskeleton rearrangement in multiple cell types. It is a chemotropic protein that is expressed within tissues and elicits both attractive and repulsive migratory responses. Netrin-1 has recently been found to modulate the immune response via the inhibition of neutrophil and macrophage migration. However, the ability of Netrin-1 to interact with lymphocytes and its in-depth effects on leukocyte migration are poorly understood...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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