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Genetic control of neuronal circuit assembly in the spinal cord

English title Genetic control of neuronal circuit assembly in the spinal cord
Applicant Arber Silvia
Number 125973
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Zellbiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2009 - 31.03.2012
Approved amount 840'000.00
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Keywords (5)

neuronal circuit formation; spinal cord; connectivity; genetic control; neuronal specification

Lay Summary (English)

Lead
Lay summary
The organization and function of the mature nervous system relies on the precision with which defined neuronal circuits are assembled into functional units during development. The aim of our studies is to understand the molecular and mechanistic basis involved in the establishment of specific connections within defined circuits of interconnected neurons. To address these questions, the main focus of our projects is on the molecular and cellular mechanisms controlling the specification of neuronal circuits in the developing vertebrate spinal cord. The spinal reflex circuit is perhaps the best-studied circuit in the context of what is known about the early steps of differentiation and about the established connectivity in the mature circuit. It therefore represents an ideal system to study molecular and cellular principles specifying selective connectivity between neuronal subtypes in vertebrates, which is ultimately of key importance to understand the function of neuronal networks.

The major focus of our research for the next several years will be on the establishment of connectivity in the spinal cord. Our previous work provides molecular and genetic entry points to approach questions of selective synaptic connectivity in the future. Future work will approach molecular and cellular events leading to specific connectivity from multiple different angles, aiming at pushing the analysis to the level of connectivity between defined functional units of the nervous system. These approaches have the common goal to identify principles governing the establishment of connectivity at the level of single neurons and their synapses in a defined vertebrate neuronal circuit during development. In the longer term, we hope to expand our acquired knowledge to neuronal circuits interconnected with spinal circuitry. To unravel the molecular cascades of genes controlling neuronal circuit formation, we combine techniques such as gain- and loss-of-function mouse genetics, light microscope imaging of fluorescently labeled neuronal subpopulations, electrophysiological analysis and gene expression profiling.

Contact details and further information can be found at:http://www.biozentrum.unibas.ch/arber/index.html
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by Modulating BMP Signaling
Ma CHE, Brenner GJ, Omura T, Samad OA, Costigan M, Inquimbert P, Niederkofler V, Salie R, Sun CC, Lin HY, Arber S, Coppola G, Woolf CJ, Samad TA (2011), The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by Modulating BMP Signaling, in JOURNAL OF NEUROSCIENCE, 31(50), 18391-18400.
Motor antagonism exposed by spatial segregation and timing of neurogenesis
Tripodi M, Stepien AE, Arber S (2011), Motor antagonism exposed by spatial segregation and timing of neurogenesis, in NATURE, 479(7371), 61-61.
Developmental neuroscience
Arber S, Davis G (2011), Developmental neuroscience, in CURRENT OPINION IN NEUROBIOLOGY, 21(1), 1-4.
Dragon (Repulsive Guidance Molecule b) Inhibits IL-6 Expression in Macrophages
Xia Y, Cortez-Retamozo V, Niederkofler V, Salie R, Chen SZ, Samad TA, Hong CC, Arber S, Vyas JM, Weissleder R, Pittet MJ, Lin HY (2011), Dragon (Repulsive Guidance Molecule b) Inhibits IL-6 Expression in Macrophages, in JOURNAL OF IMMUNOLOGY, 186(3), 1369-1376.
Monosynaptic Rabies Virus Reveals Premotor Network Organization and Synaptic Specificity of Cholinergic Partition Cells
Stepien AE, Tripodi M, Arber S (2010), Monosynaptic Rabies Virus Reveals Premotor Network Organization and Synaptic Specificity of Cholinergic Partition Cells, in NEURON, 68(3), 456-472.
Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain
Samad OA, Liu Y, Yang FC, Kramer I, Arber S, Ma QF (2010), Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain, in MOLECULAR PAIN, 6(45), 1-12.
Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells
Zimmer C, Lee J, Griveau A, Arber S, Pierani A, Garel S, Guillemot F (2010), Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells, in DEVELOPMENT, 137(2), 293-302.
Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis
Lu BC, Cebrian C, Chi X, Kuure S, Kuo R, Bates CM, Arber S, Hassell J, MacNeil L, Hoshi M, Jain S, Asai N, Takahashi M, Schmidt-Ott KM, Barasch J, D'Agati V, Costantini F (2009), Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis, in NATURE GENETICS, 41(12), 1295-1302.
Optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the Tet system
Zhu PX, Narita Y, Bundschuh ST, Fajardo O, Scharer YPZ, Chattopadhyaya B, Bouldoires EA, Stepien AE, Deisseroth K, Arber S, Sprengel R, Rijli FM, Friedrich RW (2009), Optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the Tet system, in FRONTIERS IN NEURAL CIRCUITS, 3, 1-12.
Gamma and alpha motor neurons distinguished by expression of transcription factor Err3
Friese A, Kaltschmidt JA, Ladle DR, Sigrist M, Jessell TM, Arber S (2009), Gamma and alpha motor neurons distinguished by expression of transcription factor Err3, in PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(32), 13588-13593.
Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition
Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, Arber S (2009), Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition, in NATURE, 459(7248), 842-846.
Regulation of motor circuit assembly by spatial and temporal mechanisms
Tripodi Marco, Arber Silvia, Regulation of motor circuit assembly by spatial and temporal mechanisms, in Current opinion in neurobiology.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Renshaw renewed: rules and roles of neuronal microcicuitry 05.12.2011 Rockefeller UniversityColumbia University/New York University, NY, USA
32nd Mildred Trotter Lecture 27.10.2011 Washington University in St. Louis, Missouri, USA
Inaugural Champalimaud Neuroscience Symposium 19.09.2011 Champalimaud Centre for the Unknown, Lisbon, Portugal
Biozentrum 40 Year Jubilee Symposioum 15.09.2011 Basel, Switzerland
Gordon Research Conference 2011: Neurotrophic Factors 05.06.2011 Salve Regina University, NEwport, RI, USA
13th International Neuroscience Winter Conference 29.03.2011 Soelden, Austria
Annual Meeting of the Swiss Society for Neuroscience 2011 26.03.2011 Zentrum für Lehre & Forschung, Basel, Switzerland
Society for Neuroscience 2010 Meeting "Neuroscience 2010" 13.11.2010 San diego, CA, USA
EMBO/EMBL Symposium; Structure & Function of Neuronal Circuits 05.09.2010 Heidelberg, Germany
Gordon Research Conference 2010: Neural Development 15.08.2010 Salve Regina University, Newport, RI, USA
Keystone Symosium on Molecular and Cellular Biology-Synapses: Formation, Function & Misfunction 11.04.2010 Snowbird, UTAH, USA
CCHD Program-3rd Interantional Workshop on Cell Communication in Health & Disease 17.02.2010 Center for Brain Research, Medical University of Vienna, Austria


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Donnerstagskonferenz Innere Medizin: Assistenten-DOKO 16.09.2010 Universitätsspital Basel, Switzerland


Associated projects

Number Title Start Funding scheme
112525 Genetic control of neuronal circuit assembly in the spinal cord 01.04.2006 Project funding (Div. I-III)
140625 Entwicklung und Funktion von motorischen Netzwerken 01.04.2012 Project funding (Div. I-III)

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