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J J Brudvig, J T Cain, G G Schmidt-Grimminger, D J Stumpo, K J Roux, P J Blackshear, J M Weimer
Axons of the corpus callosum (CC), the white matter tract that connects the left and right hemispheres of the brain, receive instruction from a number of chemoattractant and chemorepulsant cues during their initial navigation towards and across the midline. While it has long been known that the CC is malformed in the absence of Myristoylated alanine-rich C-kinase substrate (MARCKS), evidence for a direct role of MARCKS in axon navigation has been lacking. Here, we show that MARCKS is necessary for Netrin-1 (NTN1) signaling through the DCC receptor, which is critical for axon guidance decisions...
March 15, 2018: Molecular Neurobiology
Sofia Golenkina, Vishal Chaturvedi, Robert Saint, Michael J Murray
Netrin receptors of the DCC/NEO/UNC-40/Frazzled family have well established roles in cell migration and axon guidance but can also regulate epithelial features such as adhesion, polarity and adherens junction (AJ) stability. Previously, we have shown that overexpression of Drosophila Frazzled (Fra) in the peripodial epithelium (PE) inhibits wing disc eversion and also generates cellular protrusions typical of motile cells. Here, we tested whether the molecular pathways by which Fra inhibits eversion are distinct from those driving motility...
2018: PloS One
Christiana Martin, Young-Eun Cho, Hyungsuk Kim, Sijung Yun, Rebekah Kanefsky, Hyunhwa Lee, Vincent Mysliwiec, Ann Cashion, Jessica Gill
Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6)...
January 1, 2018: Biological Research for Nursing
Jing Peng, Ivan J Santiago, Curie Ahn, Burak Gur, C Kimberly Tsui, Zhixiao Su, Chundi Xu, Aziz Karakhanyan, Marion Silies, Matthew Y Pecot
Laminar arrangement of neural connections is a fundamental feature of neural circuit organization. Identifying mechanisms that coordinate neural connections within correct layers is thus vital for understanding how neural circuits are assembled. In the medulla of the Drosophila visual system neurons form connections within ten parallel layers. The M3 layer receives input from two neuron types that sequentially innervate M3 during development. Here we show that M3-specific innervation by both neurons is coordinated by Drosophila Fezf (dFezf), a conserved transcription factor that is selectively expressed by the earlier targeting input neuron...
March 7, 2018: ELife
Kai Yin, Shengchun Dang, Lei Cui, Xin Fan, Rong Xie, Jianguo Qu, Mengyuan Shang, Jixiang Chen
No abstract text is available yet for this article.
March 2, 2018: Biochemical and Biophysical Research Communications
Ying Liu, Tuhin Bhowmick, Yiqiong Liu, Xuefan Gao, Haydyn D T Mertens, Dmitri I Svergun, Junyu Xiao, Yan Zhang, Jia-Huai Wang, Rob Meijers
Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds...
February 20, 2018: Neuron
Xian-Qian Li, Zhen-Xing Ren, Ke Li, Jing-Jing Huang, Zi-Tong Huang, Tian-Ran Zhou, Hong-Ying Cao, Feng-Xue Zhang, Bo Tan
Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)...
February 27, 2018: International Journal of Molecular Sciences
Mouwei Zheng, Ronghua Chen, Hongbin Chen, Yixian Zhang, Jianhao Chen, Peiqiang Lin, Quan Lan, Qilin Yuan, Yongxing Lai, Xinhong Jiang, Xiaodong Pan, Nan Liu
As a secreted axon guidance molecule, Netrin-1 has been documented to be a neuroprotective factor, which can reduce infarct volume, promote angiogenesis and anti-apoptosis after stroke in rodents. However, its role in axonal regeneration and synaptic formation after cerebral ischemic injury, and the related underlying mechanisms remain blurred. In this study, we used Adeno-associated vectors carrying Netrin-1 gene (AAV-NT-1) to up-regulate the expression level of Netrin-1 in rats' brain after middle cerebral artery occlusion (MCAO)...
2018: Frontiers in Cellular Neuroscience
Shutong Xu, Yiqiong Liu, Xiaolong Li, Ying Liu, Rob Meijers, Yan Zhang, Jia-Huai Wang
Netrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution...
2018: Cell Discovery
Andrea R Yung, Noah R Druckenbrod, Jean-François Cloutier, Zhuhao Wu, Marc Tessier-Lavigne, Lisa V Goodrich
During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery...
February 13, 2018: Cell Reports
Peter Weinberg, Matthew Berkseth, David Zarkower, Oliver Hobert
Nervous systems display intriguing patterns of sexual dimorphisms across the animal kingdom, but the mechanisms that generate such dimorphisms remain poorly characterized. In the nematode Caenorhabditis elegans, a number of neurons present in both sexes are synaptically connected to one another in a sexually dimorphic manner as a result of sex-specific synaptic pruning and maintenance [1-3]. We define here a mechanism for the male-specific maintenance of the synaptic connections of the phasmid sensory neuron PHB and its male-specific target, the sex-shared AVG interneuron...
February 2, 2018: Current Biology: CB
Kyeong Seok Kim, Hyun-Jung Lim, Jong Seung Lim, Ji Yeon Son, Jaewon Lee, Byung Mu Lee, Seung Chul Chang, Hyung Sik Kim
Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague-Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl2, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl2 (25 mg/kg, oral) for 7 days...
February 5, 2018: Food and Chemical Toxicology
Huai Huang, Tao Yang, Qiangqiang Shao, Tanushree Majumder, Kristopher Mell, Guofa Liu
Heterozygous missense mutations in human TUBB3 gene result in a spectrum of brain malformations associated with defects in axon guidance, neuronal migration and differentiation. However, the molecular mechanisms underlying mutation-related axon guidance abnormalities are unclear. Recent studies have shown that netrin-1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor deleted in colorectal cancer (DCC). Furthermore, TUBB3 is required for netrin-1-induced axon outgrowth, branching and pathfinding...
January 27, 2018: Neuroscience
Meili Liu, Zhengtai Jia, Xiongfu Xiao, Zhifa Zhang, Ping Li, Gang Zhou, Yubo Fan
Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the neuronal guidance growth are still not reported. In the present study, graphene oxide (GO) and Carboxylated graphene oxide (GO-COOH) were used to investigate the potential effects on axonal guidance growth in the primary cultured cortical neurons. In addition,we characterized the structure and chemical composition of synthesized graphene oxide (GO) and carboxylated graphene oxide (GO-COOH) using Fourier transform infrared (FT-IR) spectrophotometer and Scanning Electron Microscope (SEM) assays and Raman analysis...
January 29, 2018: Journal of Biomedical Materials Research. Part A
Fabio L Urbina, Shawn M Gomez, Stephanie L Gupton
Neurite elongation and branching in developing neurons requires plasmalemma expansion, hypothesized to occur primarily via exocytosis. We posited that exocytosis in developing neurons and nonneuronal cells would exhibit distinct spatiotemporal organization. We exploited total internal reflection fluorescence microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and developed computer-vision software and statistical tools to uncover spatiotemporal aspects of exocytosis...
January 19, 2018: Journal of Cell Biology
Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Heike Blockus, Chloé Dominici, Pavol Zelina, Patrick Mehlen, Alain Chédotal
During the development of the central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about the cellular and molecular mechanisms that control the development of a boundary at the CNS surface and prevent CNS neuron emigration from the neural tube. It has previously been shown that a subset of spinal cord commissural axons abnormally invades sensory nerves in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin 1 also plays a similar role in the brain is unknown...
January 17, 2018: Development
Jiao Liu, Jianbin Bi, Zeliang Li, Zhenhua Li, Xiankui Liu, Chuize Kong
miR‑214 has been reported to be downregulated in several cancer types, such as bladder cancer. However, its involvement in apoptosis and chemoresistance has not been investigated. The present study aimed to clarify the biological function of miR‑214 and potential mechanisms in chemoresistance of bladder cancer cells. Reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑214 was downregulated in bladder cancer tissues compared with the level in normal tissues. miR‑214 was downregulated in bladder cancer cell lines compared with the level in the normal cell line SV‑HUC‑1...
January 10, 2018: International Journal of Molecular Medicine
Ying-Li Luo, Cong-Fei Xu, Hong-Jun Li, Zhi-Ting Cao, Jing Liu, Ji-Long Wang, Xiao-Jiao Du, Xian-Zhu Yang, Zhen Gu, Jun Wang
The CRISPR/Cas9 gene editing technology holds promise for the treatment of multiple diseases. However, the inability to perform specific gene editing in targeted tissues and cells, which may cause off-target effects, is one of the critical bottlenecks for therapeutic application of CRISPR/Cas9. Herein, macrophage-specific promoter-driven Cas9 expression plasmids (pM458 and pM330) were constructed and encapsulated in cationic lipid-assisted PEG-b-PLGA nanoparticles (CLAN). The obtained nanoparticles encapsulating the CRISPR/Cas9 plasmids were able to specifically express Cas9 in macrophages as well as their precursor monocytes both in vitro and in vivo...
January 9, 2018: ACS Nano
Braian M Beker, Mateo G Corleto, Cecilia Fieiras, Carlos G Musso
Acute kidney injury (AKI) consists of a rapid renal function decline which usually increases serum urea and creatinine levels. Since kidney injury begins by inducing biological and molecular changes which evolve to cellular damage, biomarkers could be used as tools for monitoring early AKI appearance, and predicting its recovery. Among the main AKI biomarkers the neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1, monocyte chemotactic peptide-1, N-acetyl-β-D-glucosaminidase, interleukin-18, liver-type fatty acid-binding protein, netrin-1, cycle arrest markers, endogenous ouabain, selenium-binding protein 1, and BPIFA2 marker, have been described...
January 6, 2018: International Urology and Nephrology
Kai Yin, Shengchun Dang, Lei Cui, Xin Fan, Rong Xie, Jianguo Qu, Mengyuan Shang, Jixiang Chen
Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect...
January 3, 2018: Biochemical and Biophysical Research Communications
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