Axon Guidance I
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Understanding Axon Guidance: Are We Nearly There Yet?
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2018 Understanding axon guidance: are we nearly there yet? Stoeckli, Esther T Abstract: During nervous system development, neurons extend axons to reach their targets and form functional circuits. The faulty assembly or disintegration of such circuits results in disorders of the nervous system. Thus, understanding the molecular mechanisms that guide axons and lead to neural circuit formation is of interest not only to developmental neuroscientists but also for a better comprehension of neural disorders. Recent studies have demonstrated how crosstalk between different families of guidance receptors can regulate axonal navigation at choice points, and how changes in growth cone behaviour at intermediate targets require changes in the surface expression of receptors. These changes can be achieved by a variety of mechanisms, including transcription, translation, protein-protein interactions, and the specific trafficking of proteins and mRNAs. Here, I review these axon guidance mechanisms, highlighting the most recent advances in the field that challenge the textbook model of axon guidance. DOI: https://doi.org/10.1242/dev.151415 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-166034 Journal Article Published Version Originally published at: Stoeckli, Esther T (2018). Understanding axon guidance: are we nearly there yet? Development, 145(10):dev151415. DOI: https://doi.org/10.1242/dev.151415 © 2018. Published by The Company of Biologists Ltd | Development (2018) 145, dev151415. doi:10.1242/dev.151415 REVIEW Understanding axon guidance: are we nearly there yet? Esther T. -
Department of Pharmacology (GRAD) 1
Department of Pharmacology (GRAD) 1 faculty participate fully at all levels. The department has the highest DEPARTMENT OF level of NIH funding of all pharmacology departments and a great diversity of research areas is available to trainees. These areas PHARMACOLOGY (GRAD) include cell surface receptors, G proteins, protein kinases, and signal transduction mechanisms; neuropharmacology; nucleic acids, cancer, Contact Information and antimicrobial pharmacology; and experimental therapeutics. Cell and molecular approaches are particularly strong, but systems-level research Department of Pharmacology such as behavioral pharmacology and analysis of knock-in and knock-out Visit Program Website (http://www.med.unc.edu/pharm/) mice is also well-represented. Excellent physical facilities are available for all research areas. Henrik Dohlman, Chair Students completing the training program will have acquired basic The Department of Pharmacology offers a program of study that leads knowledge of pharmacology and related fields, in-depth knowledge in to the degree of doctor of philosophy in pharmacology. The curriculum is their dissertation research area, the ability to evaluate scientific literature, individualized in recognition of the diverse backgrounds and interests of mastery of a variety of laboratory procedures, skill in planning and students and the broad scope of the discipline of pharmacology. executing an important research project in pharmacology, and the ability The department offers a variety of research areas including to communicate results, analysis, and interpretation. These skills provide a sound basis for successful scientific careers in academia, government, 1. Receptors and signal transduction or industry. 2. Ion channels To apply to BBSP, students must use The Graduate School's online 3. -
Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?
biomolecules Review Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison? Rosa Manzoli 1,2,†, Lorenzo Badenetti 1,3,4,†, Michela Rubin 1 and Enrico Moro 1,* 1 Department of Molecular Medicine, University of Padova, 35121 Padova, Italy; [email protected] (R.M.); [email protected] (L.B.); [email protected] (M.R.) 2 Department of Biology, University of Padova, 35121 Padova, Italy 3 Department of Women’s and Children’s Health, University of Padova, 35121 Padova, Italy 4 Pediatric Research Institute “Città della Speranza”, 35127 Padova, Italy * Correspondence: [email protected]; Tel.: +39-04-98276341 † These authors contributed equally to this paper. Abstract: Axonal trajectories and neural circuit activities strongly rely on a complex system of molec- ular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely un- derstood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases. Citation: Manzoli, R.; Badenetti, L.; Keywords: axon guidance; lysosomal storage disorders; neuronal circuit Rubin, M.; Moro, E. Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison? Biomolecules 2021, 11, 191. -
Retinal Ganglion Cell Axon Sorting at the Optic Chiasm Requires Dystroglycan
bioRxiv preprint doi: https://doi.org/10.1101/286005; this version posted March 21, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Retinal Ganglion Cell Axon Sorting at the Optic Chiasm Requires Dystroglycan Reena Clements1 and Kevin M. Wright1,2, # 1) Neuroscience Graduate Program, 2) Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA #) Correspondence to Kevin M. Wright ([email protected]). Vollum Institute, 3181 SW Sam Jackson Park Rd L474 Portland, OR 97239. (503)-494-6955 Running title: Dystroglycan regulates RGC sorting Key Words: dystroglycan, axon, optic chiasm, retina, basement membrane, extracellular matrix bioRxiv preprint doi: https://doi.org/10.1101/286005; this version posted March 21, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Summary Statement 2 Abnormal retinal ganglion cell axon sorting in the optic chiasm in the absence of 3 functional dystroglycan results in profound defects in retinorecipient innervation. 4 5 Abstract 6 In the developing visual system, retinal ganglion cell (RGC) axons project 7 from the retina to several distal retinorecipient regions in the brain. Several 8 molecules have been implicated in guiding RGC axons in vivo, but the role of 9 extracellular matrix molecules in this process remains poorly understood. 10 Dystroglycan is a laminin-binding transmembrane protein important for formation 11 and maintenance of the extracellular matrix and basement membranes and has 12 previously been implicated in axon guidance in the developing spinal cord. -
UNC-45A Is a Novel Microtubule-Associated Protein And
Published OnlineFirst October 15, 2018; DOI: 10.1158/1541-7786.MCR-18-0670 Cell Cycle and Senescence Molecular Cancer Research UNC-45A Is a Novel Microtubule-Associated Protein and Regulator of Paclitaxel Sensitivity in Ovarian Cancer Cells Ashley Mooneyham1, Yoshie Iizuka1, Qing Yang2, Courtney Coombes2, Mark McClellan2, Vijayalakshmi Shridhar3, Edith Emmings1, Mihir Shetty1, Liqiang Chen4, Teng Ai4, Joyce Meints5, Michael K. Lee5, Melissa Gardner2, and Martina Bazzaro1 Abstract UNC-45A, a highly conserved member of the UCS congression and segregation. UNC-45A is overexpressed in (UNC45A/CRO1/SHE4P) protein family of cochaperones, human clinical specimens from chemoresistant ovarian plays an important role in regulating cytoskeletal-associat- cancer and that UNC-45A–overexpressing cells resist chro- ed functions in invertebrates and mammalian cells, includ- mosome missegregation and aneuploidy when treated with ing cytokinesis, exocytosis, cell motility, and neuronal clinically relevant concentrations of paclitaxel. Lastly, development. Here, for the first time, UNC-45A is demon- UNC-45A depletion exacerbates paclitaxel-mediated stabi- strated to function as a mitotic spindle-associated protein lizing effects on mitotic spindles and restores sensitivity to that destabilizes microtubules (MT) activity. Using in vitro paclitaxel. biophysicalreconstitutionandtotalinternalreflection fluo- rescence microscopy analysis, we reveal that UNC-45A Implications: These findings reveal novel and significant directly binds to taxol-stabilized MTs in the absence of any roles for UNC-45A in regulation of cytoskeletal dynamics, additional cellular cofactors or other MT-associated pro- broadening our understanding of the basic mechanisms teins and acts as an ATP-independent MT destabilizer. In regulating MT stability and human cancer susceptibility to cells, UNC-45A binds to and destabilizes mitotic spindles, paclitaxel, one of the most widely used chemotherapy and its depletion causes severe defects in chromosome agents for the treatment of human cancers. -
Master Layout Sheet
2893 REVIEW ARTICLE CANADIAN ASSOCIATION OF NEUROSCIENCES REVIEW: Postnatal Development of the Mammalian Neocortex: Role of Activity Revisited Zhong-wei Zhang ABSTRACT: The mammalian neocortex is the largest structure in the brain, and plays a key role in brain function. A critical period for the development of the neocortex is the early postnatal life, when the majority of synapses are formed and when much of synaptic remodeling takes place. Early studies suggest that initial synaptic connections lack precision, and this rudimentary wiring pattern is refined by experience-related activity through selective elimination and consolidation. This view has been challenged by recent studies revealing the presence of a relatively precise pattern of connections before the onset of sensory experience. The recent data support a model in which specificity of neuronal connections is largely determined by genetic factors. Spontaneous activity is required for the formation of neural circuits, but whether it plays an instructive role is still controversial. Neurotransmitters including acetylcholine, serotonin, and γ-Aminobutyric acid (GABA) may have key roles in the regulation of spontaneous activity, and in the maturation of synapses in the developing brain. RÉSUMÉ: Développement postnatal du néocortex chez les mammifères: révision du rôle de l’activité. Le néocortex des mammifères est la plus grosse structure du cerveau et il joue un rôle stratégique dans la fonction cérébrale. La période postnatale est critique pour son développement. La majorité des synapses se forment à ce moment-là ainsi qu’une grande partie du remodelage synaptique. Plusieurs études ont suggéré que les connections synaptiques initiales manquent de précision et que ce « câblage » rudimentaire du cerveau est raffiné par l’activité reliée à l’expérience, par élimination et consolidation sélective. -
Cell Adhesion Or Integrin Clustering Increases Phosphorylation of A
THEJOURNAL OF BIOLOGICALCHEMISTRY Vol. 267, No. 33, Issue,of November 25, pp. 23439-23442,1992 Communication 0 1992 hy The American Society for Blochemistry and Molecular Biology, Inc. Printed in U.S.A. Evidence from several laboratories suggest that integrins Cell Adhesionor Integrin may transmit biochemical signals from the extracellular ma- Clustering Increases trix to theinterior of the cell. Consistent with this notion are Phosphorylation of a Focal the observations that interactions of integrins with their Adhesion-associated Tyrosine protein ligands can modulate intracellular pH (11, 121, acti- vation of T-lymphocytes (13, 14) and neutrophils (15), tu- Kinase" morigenicity (16, 17), and gene expression in fibroblasts (18) (Received for publication, July 29, 1992) and monocytes (19-21). Our laboratory has recently reported that clustering of Dl integrins on human carcinoma cells with Lori KornbergS, H. Shelton EarpO, anti-integrin antibodies leads to enhanced phosphorylation J. Thomas Parsonsn, Michael Schallerv, and R. L. JulianoS on tyrosine residues of a complex of proteins with molecular weights of 113,000-130,000 (22). This observation has been From the $Department of Pharmacology, 9Lineberger Comprehensive Cancer Center, Universityof North confirmed by others who have shown that adhesion of 3T3 Carolina, Chapel Hill,North Carolina 27599 and the fibroblasts and chicken embryo fibroblasts to fibronectin in- YDepartment of Microbiology, University of Virginia, duces tyrosine phosphorylation of a 120-kDa protein (23) as Charlottesville, Virginia22908 well as thefocal adhesion-associated protein paxillin.' A 125-kDa focal adhesion-associated tyrosine kinase We have recently shown that changes in tyrosine (~125'"') was recently described (24, 25). ~125''~was initially phosphorylation of a 130-kDa protein(s) (pp130) may identified as being one of several proteins that were highly be involved inintegrin signaling (Kornberg, L., Earp, phosphorylated in src-transformed chicken embryo fibro- H. -
ONCOGENOMICS Deaths in the United States and Other Developed 2000)
Oncogene (2002) 21, 3814 ± 3825 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Identi®cation of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis Chaitanya S Bangur*,1, Ann Switzer1, Liqun Fan1, Matthew J Marton2, Michael R Meyer2 and Tongtong Wang1 1Tumor Antigen Discovery, Corixa Corporation, 1124 Columbia Street, Seattle, Washington WA 98104, USA; 2Rosetta Inpharmatics, 12040 115th Avenue NE, Kirkland, Washington, WA 98034, USA To identify genes that are dierentially over-expressed in rate for patients diagnosed with NSCLC is 10 ± 15%, Small Cell Lung Carcinoma (SCLC) we have used a while patients diagnosed with SCLC have an even combination of suppression subtractive hybridization and worse prognosis with a 5-year survival rate of 55% cDNA microarray to analyse the expression pro®les of (Ginsberg et al., 1997; Ihde et al., 1997). Although, 2400 cDNAs clones. Genes that are over-expressed in SCLC is initially highly responsive to radiation and SCLC were identi®ed using 32 pairs of ¯uorescence- chemotherapy (50 ± 90%), most patients tend to relapse labeled cDNA samples representing various lung tumors with highly resistant disease within a year of treatment and normal tissues. This comprehensive approach has (Ihde et al., 1997). Most patients diagnosed with SCLC resulted in the identi®cation of 209 genes that are have regional lymph-node involvement or disseminated dierentially over-expressed in SCLC. Quantitative real- disease at the time of initial diagnosis (Ihde, 1992), time PCR was used to further validate the expression of which strongly correlates with the poor prognosis 43 genes in SCLC tumors and various normal tissues. -
Sustained Expression of Unc-4 Homeobox Gene and Unc-37/Groucho in Postmitotic Neurons Specifies the Spatial Organization of the Cholinergic Synapses in C
RESEARCH ARTICLE Sustained expression of unc-4 homeobox gene and unc-37/Groucho in postmitotic neurons specifies the spatial organization of the cholinergic synapses in C. elegans Mizuki Kurashina1,2, Jane Wang1, Jeffrey Lin1, Kathy Kyungeun Lee1, Arpun Johal1, Kota Mizumoto1,2,3,4* 1Department of Zoology, University of British Columbia, Vancouver, Canada; 2Graduate Program in Cell and Developmental Biology, University of British Columbia, Vancouver, Canada; 3Life Sciences Institute, University of British Columbia, Vancouver, Canada; 4Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada Abstract Neuronal cell fate determinants establish the identities of neurons by controlling gene expression to regulate neuronal morphology and synaptic connectivity. However, it is not understood if neuronal cell fate determinants have postmitotic functions in synapse pattern formation. Here we identify a novel role for UNC-4 homeobox protein and its corepressor UNC-37/ Groucho, in tiled synaptic patterning of the cholinergic motor neurons in Caenorhabditis elegans. We show that unc-4 is not required during neurogenesis but is required in the postmitotic neurons for proper synapse patterning. In contrast, unc-37 is required in both developing and postmitotic neurons. The synaptic tiling defects of unc-4 mutants are suppressed by bar-1/b-catenin mutation, which positively regulates the expression of ceh-12/HB9. Ectopic ceh-12 expression partly underlies the synaptic tiling defects of unc-4 and unc-37 mutants. Our results reveal a novel postmitotic role *For correspondence: [email protected] of neuronal cell fate determinants in synapse pattern formation through inhibiting the canonical Wnt signaling pathway. Competing interests: The authors declare that no competing interests exist. -
The Caenorhabditis Elegans Unc-13 Gene Product Is a Phospholipid-Dependent High-Affinity Phorbol Ester Receptor
Biochem. J. (1992) 287, 995-999 (Printed in Great Britain) 995 The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor Sohail AHMED,*t§ Ichiro N. MARUYAMA, II Robert KOZMA,*t Joel LEE,*t Sydney BRENNERt and Louis LIM*t *Institute of Molecular and Cell Biology, National University of Singapore, Singapore 0511, tDepartment of Neurochemistry, Institute of Neurology, 1 Wakefield St., London WC1N 1PJ, U.K., and tMedical Research Council Molecular Genetics Unit, Hills Road, Cambridge CB2 2QH, U.K. The Caenorhabditis elegans unc-13 mutant is a member of a class of mutants that have un-coordinated movement. Mutations of the unc-13 gene cause diverse defects in C. elegans, including abnormal neuronal connections and modified synaptic transmission in the nervous system. unc-13 cDNA encodes a protein (UNC-13) of 1734 amino acid residues with a predicted molecular mass of 198 kDa and sequence identity to the C1/C2 regions but not to the catalytic domain of the ubiquitously expressed protein kinase C family [Maruyama & Brenner (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5729-5733]. To characterize the phorbol ester binding site of the UNC- 13 protein, cDNA encoding the Cl /C2-like regions (amino acid residues 546-940) was expressed in Escherichia coli and the 43 kDa recombinant protein was purified. Phorbol ester binding to the 43 kDa protein was zinc- and phospholipid-dependent, stereospecific and of high affinity (Kd 67 nM). UNC-13 specific antisera detected a protein of approx. 190 kDa in wild-type (N2) but not in mutant (eJO19) C. -
Molecular Regulation of Visual System Development: More Than Meets the Eye
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Molecular regulation of visual system development: more than meets the eye Takayuki Harada,1,2 Chikako Harada,1,2 and Luis F. Parada1,3 1Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA; 2Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan Vertebrate eye development has been an excellent model toderm, intercalating mesoderm, surface ectoderm, and system to investigate basic concepts of developmental neural crest (Fig. 1). The neuroectoderm differentiates biology ranging from mechanisms of tissue induction to into the retina, iris, and optic nerve; the surface ecto- the complex patterning and bidimensional orientation of derm gives rise to lens and corneal epithelium; the me- the highly specialized retina. Recent advances have shed soderm differentiates into the extraocular muscles and light on the interplay between numerous transcriptional the fibrous and vascular coats of the eye; and neural crest networks and growth factors that are involved in the cells become the corneal stroma sclera and corneal en- specific stages of retinogenesis, optic nerve formation, dothelium. The vertebrate eye originates from bilateral and topographic mapping. In this review, we summarize telencephalic optic grooves. In humans, optic vesicles this recent progress on the molecular mechanisms un- emerge at the end of the fourth week of development and derlying the development of the eye, visual system, and soon thereafter contact the surface ectoderm to induce embryonic tumors that arise in the optic system. -
CELF RNA Binding Proteins Promote Axon Regeneration in C. Elegans and Mammals 1 Through Alternative Splicing of Syntaxins 2 Lizh
1 CELF RNA binding proteins promote axon regeneration in C. elegans and mammals 2 through alternative splicing of Syntaxins 3 Lizhen Chen1,2,§, Zhijie Liu3, Bing Zhou4, Chaoliang Wei4, Yu Zhou4, Michael G. Rosenfeld2,3, 4 Xiangdong Fu4, Andrew D. Chisholm1,*, Yishi Jin1,2,4,* 5 6 1 Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, 7 La Jolla, CA92093 8 2 Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 9 92093 10 3 Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 11 92093 12 4 Department of Cellular and Molecular Medicine, School of Medicine, University of California, 13 San Diego, La Jolla, CA 92093 14 15 * to whom correspondence should be addressed 16 § Current address: Barshop Institute for Longevity and Aging Studies, Department of Cellular 17 and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, 18 Texas 78245 19 With 7 Figures, 3 Videos, 9 figure supplements, 7 Supplementary Files 20 Key words: UNC-75, CLIP-seq, alternative splicing, SNARE, DRG, CUGBP, ETR3 21 1 22 Abstract 23 Axon injury triggers dramatic changes in gene expression. While transcriptional regulation 24 of injury-induced gene expression is widely studied, less is known about the roles of RNA 25 binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. 26 elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon 27 regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) 28 we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75.