scholarly journals Single-cell transcriptomic analysis of the adult mouse spinal cord

2020 ◽  
Author(s):  
Jacob A. Blum ◽  
Sandy Klemm ◽  
Lisa Nakayama ◽  
Arwa Kathiria ◽  
Kevin A. Guttenplan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Single Cell ◽  
Motor Neurons ◽  
The Body ◽  
Molecular Heterogeneity ◽  
Spinal Motor Neuron ◽  
Spinal Motor ◽  
Full Complement ◽  
Adult Spinal Cord

AbstractThe spinal cord is a fascinating structure responsible for coordinating all movement in vertebrates. Spinal motor neurons control the activity of virtually every organ and muscle throughout the body by transmitting signals that originate in the spinal cord. These neurons are remarkably heterogeneous in their activity and innervation targets. However, because motor neurons represent only a small fraction of cells within the spinal cord and are difficult to isolate, the full complement of motor neuron subtypes remains unknown. Here we comprehensively describe the molecular heterogeneity of motor neurons within the adult spinal cord. We profiled 43,890 single-nucleus transcriptomes using fluorescence-activated nuclei sorting to enrich for spinal motor neuron nuclei. These data reveal a transcriptional map of the adult mammalian spinal cord and the first unbiased characterization of all transcriptionally distinct autonomic and somatic spinal motor neuron subpopulations. We identify 16 sympathetic motor neuron subtypes that segregate spatially along the spinal cord. Many of these subtypes selectively express specific hormones and receptors, suggesting neuromodulatory signaling within the autonomic nervous system. We describe skeletal motor neuron heterogeneity in the adult spinal cord, revealing numerous novel markers that distinguish alpha and gamma motor neurons—cell populations that are specifically affected in neurodegenerative disease. We also provide evidence for a novel transcriptional subpopulation of skeletal motor neurons. Collectively, these data provide a single-cell transcriptional atlas for investigating motor neuron diversity as well as the cellular and molecular basis of motor neuron function in health and disease.

The zebrafish detour gene is essential for cranial but not spinal motor neuron induction

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2727-2737 ◽  
Author(s):  
A. Chandrasekhar ◽  
H.E. Schauerte ◽  
P. Haffter ◽  
J.Y. Kuwada
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Spinal Motor Neuron ◽  
Neuronal Phenotype ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Hh Signaling ◽  
Function Cell

The zebrafish detour (dtr) mutation generates a novel neuronal phenotype. In dtr mutants, most cranial motor neurons, especially the branchiomotor, are missing. However, spinal motor neurons are generated normally. The loss of cranial motor neurons is not due to aberrant hindbrain patterning, failure of neurogenesis, increased cell death or absence of hh expression. Furthermore, activation of the Hh pathway, which normally induces branchiomotor neurons, fails to induce motor neurons in the dtr hindbrain. Despite this, not all Hh-mediated regulation of hindbrain development is abolished since the regulation of a neural gene by Hh is intact in the dtr hindbrain. Finally, dtr can function cell autonomously to induce branchiomotor neurons. These results suggest that detour encodes a component of the Hh signaling pathway that is essential for the induction of motor neurons in the hindbrain but not in the spinal cord and that dtr function is required for the induction of only a subset of Hh-mediated events in the hindbrain.

scholarly journals The pathogenic role of c-Kit+ mast cells in the spinal motor neuron-vascular niche in ALS

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariángeles Kovacs ◽  
Catalina Alamón ◽  
Cecilia Maciel ◽  
Valentina Varela ◽  
Sofía Ibarburu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mast Cells ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Immune Cells ◽  
Spinal Cord Tissue ◽  
Cell Reactivity ◽  
Spinal Motor Neuron ◽  
Spinal Motor ◽  
Vascular Niche

AbstractDegeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues. Upon activation, MCs undergo degranulation with the ability to increase vascular permeability, orchestrate neuroinflammation and modulate the neuroimmune response. However, the prevalence, pathological significance, and pharmacology of MCs in the CNS of ALS patients remain largely unknown. In autopsy ALS spinal cords, we identified for the first time that MCs express c-Kit together with chymase, tryptase, and Cox-2 and display granular or degranulating morphology, as compared with scarce MCs in control cords. In ALS, MCs were mainly found in the niche between spinal motor neuron somas and nearby microvascular elements, and they displayed remarkable pathological abnormalities. Similarly, MCs accumulated in the motor neuron-vascular niche of ALS murine models, in the vicinity of astrocytes and motor neurons expressing the c-Kit ligand stem cell factor (SCF), suggesting an SCF/c-Kit-dependent mechanism of MC differentiation from precursors. Mechanistically, we provide evidence that fully differentiated MCs in cell cultures can be generated from the murine ALS spinal cord tissue, further supporting the presence of c-Kit+ MC precursors. Moreover, intravenous administration of bone marrow-derived c-Kit+ MC precursors infiltrated the spinal cord in ALS mice but not in controls, consistent with aberrant trafficking through a defective microvasculature. Pharmacological inhibition of c-Kit with masitinib in ALS mice reduced the MC number and the influx of MC precursors from the periphery. Our results suggest a previously unknown pathogenic mechanism triggered by MCs in the ALS motor neuron-vascular niche that might be targeted pharmacologically.

scholarly journals Slit/Robo signals prevent spinal motor neuron emigration by organizing the spinal cord basement membrane

2019 ◽  
Author(s):  
Minkyung Kim ◽  
Clare H Lee ◽  
Sarah J Barnum ◽  
Roland CJ Watson ◽  
Jennifer Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Basement Membrane ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Tube ◽  
Spinal Motor Neuron ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Ventral Neural Tube ◽  
Set Up

AbstractThe developing spinal cord builds a boundary between the CNS and the periphery, in the form of a basement membrane. The spinal cord basement membrane is a barrier that retains CNS neuron cell bodies, while being selectively permeable to specific axon types. Spinal motor neuron cell bodies are located in the ventral neural tube next to the floor plate and project their axons out through the basement membrane to peripheral targets. However, little is known about how spinal motor neuron cell bodies are retained inside the ventral neural tube, while their axons can exit. In previous work, we found that disruption of Slit/Robo signals caused motor neuron emigration outside the spinal cord. In the current study, we investigate how Slit/Robo signals are necessary to keep spinal motor neurons within the neural tube. Our findings show that when Slit/Robo signals were removed from motor neurons, they migrated outside the spinal cord. Furthermore, this emigration was associated with abnormal basement membrane protein expression in the ventral spinal cord. Using Robo2 and Slit2 conditional mutants, we found that motor neuron-derived Slit/Robo signals were required to set up a normal basement membrane in the spinal cord. Together, our results suggest that motor neurons produce Slit signals that are required for the basement membrane assembly to retain motor neuron cell bodies within the spinal cord.

scholarly journals Slit/Robo signals prevent spinal motor neuron emigration by organizing the spinal cord basement membrane.

2019 ◽  
Vol 455 (2) ◽  
pp. 449-457
Author(s):  
Minkyung Kim ◽  
Clare H. Lee ◽  
Sarah J. Barnum ◽  
Roland CJ. Watson ◽  
Jennifer Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Basement Membrane ◽  
Motor Neuron ◽  
Spinal Motor Neuron ◽  
Spinal Motor

(−)-Deprenyl Attenuates Spinal Motor Neuron Degeneration and Associated Locomotor Deficits in Rats Subjected to Spinal Cord Ischemia

1998 ◽  
Vol 149 (1) ◽  
pp. 123-129 ◽  
Author(s):  
R. Ravikumar ◽  
M.K. Lakshmana ◽  
B.S. Shankaranarayana Rao ◽  
B.L. Meti ◽  
P.N. Bindu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Spinal Cord Ischemia ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Spinal Motor Neuron ◽  
Spinal Motor ◽  
Locomotor Deficits

Three forms of the scratch reflex in the spinal turtle: central generation of motor patterns

1985 ◽  
Vol 53 (6) ◽  
pp. 1517-1534 ◽  
Author(s):  
G. A. Robertson ◽  
L. I. Mortin ◽  
J. Keifer ◽  
P. S. Stein
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Neuromuscular Blockade ◽  
Motor Neurons ◽  
Muscle Activity ◽  
Activity Patterns ◽  
Knee Extensor ◽  
The Body ◽  
Retractor Muscle ◽  
Neuron Activity

A turtle with a complete transection of the spinal cord, termed a spinal turtle, exhibits three types or “forms” of the scratch reflex: the rostral scratch, pocket scratch, and caudal scratch (21). Each scratch form is elicited by tactile stimulation of a site on the body surface innervated by afferents entering the spinal cord caudal to the transection. We recorded electromyographic (EMG) potentials from the hindlimb during each of the three forms of the scratch in the spinal turtle (see Fig. 1). Common to all scratch forms is the rhythmic alternation of the activity of the hip protractor muscle (VP-HP) and hip retractor muscle (HR-KF). Each form of the scratch displays a characteristic timing of the activity of the knee extensor muscle (FT-KE) with respect to the cycle of activity of the hip muscles VP-HP and HR-KF. In a rostral scratch, activation of FT-KE occurs during the latter portion of VP-HP activation. In a pocket scratch, activation of FT-KE occurs during HR-KF activation. In a caudal scratch, activation of FT-KE occurs after the cessation of HR-KF activation. The timing characteristics of these muscle activity patterns correspond to the timing characteristics of changes in the angles of the knee joint and the hip joint obtained with movement analyses (21). We recorded electroneurographic (ENG) potentials from peripheral nerves of the hindlimb during each of the three forms of the “fictive” scratch in the spinal turtle immobilized with neuromuscular blockade (see Fig. 4). Common to all forms of the fictive scratch is the rhythmic alternation of the activity of hip protractor motor neurons (VP-HP) and hip retractor motor neurons (HR-KF). Each form displays a characteristic timing of the activity of knee extensor motor neurons (FT-KE) with respect to the cycle of VP-HP and HR-KF motor neuron activity. The timing characteristics of these motor neuron activity patterns are similar to the timing characteristics of the muscle activity patterns obtained in the preparation with movement (cf. Figs. 1 and 4). The motor pattern for each scratch form is generated centrally within the spinal cord. In the spinal immobilized preparation, neuromuscular blockade prevents both limb movement and phasic sensory input, and complete spinal transection isolates the cord from supraspinal input.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Illuminating ALS Motor Neurons With Optogenetics in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Kazuhide Asakawa ◽  
Hiroshi Handa ◽  
Koichi Kawakami
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Rna Binding ◽  
The Body ◽  
Optical Methods ◽  
Light Illumination ◽  
Whole Cells ◽  
Spinal Motor Neurons ◽  
Spinal Motor

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Spinal motor neurons align along the spinal cord length within the vertebral column, and extend long axons to connect with skeletal muscles covering the body surface. Due to this anatomy, spinal motor neurons are among the most difficult cells to observe in vivo. Larval zebrafish have transparent bodies that allow non-invasive visualization of whole cells of single spinal motor neurons, from somas to the neuromuscular synapses. This unique feature, combined with its amenability to genome editing, pharmacology, and optogenetics, enables functional analyses of ALS-associated proteins in the spinal motor neurons in vivo with subcellular resolution. Here, we review the zebrafish skeletal neuromuscular system and the optical methods used to study it. We then introduce a recently developed optogenetic zebrafish ALS model that uses light illumination to control oligomerization, phase transition and aggregation of the ALS-associated DNA/RNA-binding protein called TDP-43. Finally, we will discuss how this disease-in-a-fish ALS model can help solve key questions about ALS pathogenesis and lead to new ALS therapeutics.

Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 25-36 ◽  
Author(s):  
B. Lutz ◽  
S. Kuratani ◽  
A.J. Cooney ◽  
S. Wawersik ◽  
S.Y. Tsai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Thyroid Hormone ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Orphan Receptor ◽  
Northern Analysis ◽  
Spinal Motor Neurons ◽  
Spinal Motor

Members of the steroid/thyroid hormone receptor superfamily are involved in the control of cell identity and of pattern formation during embryonic development. Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) can act as regulators of various steroid/thyroid hormone receptor pathways. To begin to study the role of COUP-TFs during embryogenesis, we cloned a chicken COUP-TF (cCOUP-TF II) which is highly homologous to human COUP-TF II. Northern analysis revealed high levels of cCOUP-TF II transcripts during organogenesis. Nuclear extracts from whole embryos and from embryonic spinal cords were used in electrophoretic mobility shift assays. These assays showed that COUP-TF protein is present in these tissues and is capable of binding to a COUP element (a direct repeat of AGGTCA with one base pair spacing). Analysis of cCOUP-TF expression by in situ hybridization revealed high levels of cCOUP-TF II mRNA in the developing spinal motor neurons. Since the ventral properties of the spinal cord, including the development of motor neurons, is in part established by inductive signals from the notochord, we transplanted an additional notochord next to the dorsal region of the neural tube in order to induce ectopic motor neurons. We observed that an ectopic notochord induced cCOUP-TF II gene expression in the dorsal spinal cord in a region coextensive with ectopic domains of SC1 and Islet-1, two previously identified motor neuron markers. Collectively, our studies raise the possibility that cCOUP-TF II is involved in motor neuron development.

scholarly journals Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates

2021 ◽  
Author(s):  
Ee Shan Liau ◽  
Suoqin Jin ◽  
Yen-Chung Chen ◽  
Wei-Szu Liu ◽  
Luok Wen Yong ◽  
...  
Keyword(s):  
Single Cell ◽  
Motor Neurons ◽  
Classification System ◽  
Neural Basis ◽  
Spinal Motor Neuron ◽  
Sensory Stimuli ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Motor Movements ◽  
Unified Classification System

AbstractSpinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.

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