A recoverable state of axon injury persists for hours after spinal cord contusion in vivo.
Williams PR, Marincu BN, Sorbara CD, Mahler CF, Schumacher AM, Griesbeck O, Kerschensteiner M*, Misgeld T* co-senior authors*
Nat Commun.
Therapeutic strategies for spinal cord injury (SCI) commonly focus on regenerating disconnected axons. An alternative approach would be to maintain continuity of damaged axons, especially after contusion. The viability of such neuropreservative strategies depends on the degree to which initially inj ...
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Pervasive Axonal Transport Deficits in Multiple Sclerosis Models
Sorbara CD, Wagner NE, Ladwig A, Nikic I, Merkler D, Kleele T, Marinkovic P, Naumann R, Godinho L, Bareyre FM, Bishop D, Misgeld T*, Kerschensteiner M* co-senior authors*
Impaired axonal transport can contribute to axon degeneration and has been described in many neurodegenerative diseases. Multiple sclerosis (MS) is a common neuroinflammatory disease, which is characterized by progressive axon degeneration-whether, when, and how axonal transport is affected in this ...
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An assay to image neuronal microtubule dynamics in mice
Kleele T, Marinkoviæ P, Williams PR, Stern S, Weigand EE, Engerer P, Naumann R, Hartmann J, Karl RM, Bradke F, Bishop D, Herms J, Konnerth A, Kerschensteiner M, Godinho L, Misgeld T.
Nat Commun.
Microtubule dynamics in neurons play critical roles in physiology, injury and disease and determine microtubule orientation, the cell biological correlate of neurite polarization. Several microtubule binding proteins, including end-binding protein 3 (EB3), specifically bind to the growing plus tip o ...
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Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo
Breckwoldt MO, Pfister FM, Bradley PM, Marinkovic P, Williams PR, Brill MS, Plomer B, Schmalz A, St Clair DK, Naumann R, Griesbeck O, Schwarzländer M, Godinho L, Bareyre FM, Dick TP, Kerschensteiner M*, Misgeld T* Co-senior authors*
Nat. Med.
Mitochondrial redox signals have a central role in neuronal physiology and disease. Here we describe a new optical approach to measure fast redox signals with single-organelle resolution in living mice that express genetically encoded redox biosensors in their neuronal mitochondria. Moreover, we dem ...
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Cellular, subcellular and functional in vivo labeling of the spinal cord using vital dyes
Romanelli E, Sorbara CD, Nikiæ I, Dagkalis A, Misgeld T, Kerschensteiner M.
Nature Protocols
Here we provide a protocol for rapidly labeling different cell types, distinct subcellular compartments and key injury mediators in the spinal cord of living mice. This method is based on the application of synthetic vital dyes to the surgically exposed spinal cord. Suitable vital dyes applied in ap ...
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Sequential Photo-bleaching to Delineate Single Schwann Cells at the Neuromuscular Junction.
Brill MS, Marinkoviæ P, Misgeld T.
J Vis Exp.
Sequential photo-bleaching provides a non-invasive way to label individual SCs at the NMJ. The NMJ is the largest synapse of the mammalian nervous system and has served as guiding model to study synaptic structure and function. In mouse NMJs motor axon terminals form pretzel-like contact sites with ...
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In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system
Plucinska G*, Paquet, D*, Hruscha A, Godinho L, Haass C, Schmid B**, Misgeld T** Co-first authors *, Co-senior authors**
Journal of Neuroscience
Mitochondria provide ATP, maintain calcium homeostasis, and regulate apoptosis. Neurons, due to their size and complex geometry, are particularly dependent on the proper functioning and distribution of mitochondria. Thus disruptions of these organelles and their transport play a central role in a br ...
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Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis
Marinkoviæ P, Reuter MS, Brill MS, Godinho L, Kerschensteiner M* and Misgeld T*. *co-senior authors
Axonal transport deficits have been reported in many neurodegenerative conditions and are widely assumed to be an immediate causative step of axon and synapse loss. By imaging changes in axonal morphology and organelle transport over time in several animal models of amyotrophic lateral sclerosis (AL ...
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Spatial constraints dictate glial territories at neuromuscular junctions
Brill MS, Lichtman JW, Thompson W, Zuo Y* & Misgeld T*. *co-senior authors
J Cell Biol
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain ...
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Comment by B. Short

Near-infrared branding efficiently correlates light and electron microscopy.
Bishop D, Nikic I, Brinkoetter M, Knecht S, Potz S, Kerschensteiner M*, Misgeld T*. *Co-senior authors
Nature Methods
The correlation of light and electron microscopy of complex tissues remains a major challenge. Here we report near-infrared branding (NIRB), which facilitates such correlation by using a pulsed, near-infrared laser to create defined fiducial marks in three dimensions in fixed tissue. As these marks ...
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Generation and screening of mice with transgenic neuronal labeling controlled by Thy1 regulatory elements
Marinkovic P, Godinho L, Misgeld T
Imaging in Neuroscience: A Laboratory Manual. CSHL Press 2011
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A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis.
Nikiæ I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Brück W, Bishop D, Misgeld T*, Kerschensteiner M*. *Co-senior authors
Nature Medicine
In multiple sclerosis, a common inflammatory disease of the central nervous system, immune-mediated axon damage is responsible for permanent neurological deficits. How axon damage is initiated is not known. Here we use in vivo imaging to identify a previously undescribed variant of axon damage in a ...
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News and Views by M.J. Craner and L. Fugger

Live imaging of zebrafish development
Godinho L
Imaging in Developmental Biology. CSHL Press 2011
In the last couple of decades the small tropical freshwater-dwelling zebrafish has emerged as a popular model for developmental biologists. The exceptional optical accessibility of zebrafish embryos coupled with the ability to use genetic tools to indelibly tag cells have been exploi ...
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Chapouton P & Godinho L
Methods Cell Biol 2010
For more than a decade, the zebrafish has proven to be an excellent model organism to investigate the mechanisms of neurogenesis during development. The often cited advantages, namely external development, genetic, and optical accessibility, have permitted direct examination and experimental manipul ...
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A voltage-dependent inward rectifying potassium conductance in the outer membrane of neuronal mitochondria.
Fieni F, Parkar A, Misgeld T, Kerschensteiner M, Lichtman JW, Pasinelli P, Trotti D.
J Biol Chem. 2010 Jun 15.
Potassium fluxes integrate mitochondria into cellular activities, controlling their volume homeostasis and structural integrity in many pathophysiological mechanisms. The outer mitochondrial membrane (OMM) is thought to play a passive role in this process since K+ is believed to equilibrate freely b ...
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