Etv1 Inactivation Reveals Proprioceptor Subclasses that Reflect the Level of NT3 Expression in Muscle Targets

Nooij, Joriene C. de; Doobar, Staceyann; Jessell, Thomas M.

doi:10.1016/j.neuron.2013.01.015

Cited by 105 publications

(145 citation statements)

References 60 publications

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“…Images were acquired on Zeiss LSM-510 Meta confocal microscopes. Antibodies used in this study were as follows: goat anti-CTB (List Biological Laboratories), rabbit anti-tetramethylrhodamine (Invitrogen), goat anti-ChAT (Chemicon), rabbit anti-ChAT (Demireva et al, 2011), rabbit anti-VAMP 1 (Synaptic Systems), mouse anti-VAMP 2 (Synaptic Systems), Rabbit anti-VAMP 3 (Synaptic Systems), guinea pig anti-vGluT1 (Betley et al, 2009), and chicken anti-Pv (de Nooij et al, 2013). …”

Section: Methodsmentioning

confidence: 99%

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Mendelsohn

Simon

Abbott

et al. 2015

Neuron

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Summary The construction of spinal sensory-motor circuits involves the selection of appropriate synaptic partners and the allocation of precise synaptic input densities. Many aspects of spinal sensory-motor selectivity appear to be preserved when peripheral sensory activation is blocked, which has led to a view that sensory-motor circuits are assembled in an activity-independent manner. Yet it remains unclear whether activity-dependent refinement has a role in the establishment of connections between sensory afferents and those motor pools that have synergistic biomechanical functions. We show here that genetically abolishing central sensory-motor neurotransmission leads to a selective enhancement in the number and density of such “heteronymous” connections, whereas other aspects of sensory-motor connectivity are preserved. Spike-timing dependent synaptic refinement represents one possible mechanism for the changes in connectivity observed after activity blockade. Our findings therefore reveal that sensory activity does have a limited and selective role in the establishment of patterned monosynaptic sensory-motor connections.

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Section: Methodsmentioning

confidence: 99%

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Mendelsohn

Simon

Abbott

et al. 2015

Neuron

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“…This sense is detected by sensory neurons (see Box 2) such as group Ia, Ib, and II fibers that detect changes in muscle length and tension. Spinal targets of these sensory neurons, largely labeled by parvalbumin (PV) (Arber et al, 2000;de Nooij et al, 2013), include secondary neurons in spinal cord that send this information up to the cerebellum (via spinocerebellar tracts, SCTs) (Brown, 1981;Oscarsson, 1965;Yuengert et al, 2015) and motor neurons for monosynaptic reflex arcs (Arber et al, 2000). SCTs consist of an ipsilateral-projecting population (the dorsal SCT, DSCT) and a contralateral-projecting population (the ventral SCT, VSCT).…”

Section: Proprioceptionmentioning

confidence: 99%

Making sense out of spinal cord somatosensory development

2016

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The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits.

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“…Sensory neurons expressing NF200, but lacking parvalbumin are largely regarded as mechanosensitive cells, whereas those NF200 + neurons coexpressing parvalbumin are proprioceptive (26,27). Parvalbumin also labels a small population of low threshold cutaneous mechanoreceptive neurons, so there is the minor caveat that not all parvalbumin + neurons are proprioceptive (43). Small area, peripherin-expressing neurons can also be divided into nonpeptidergic, principally mechanical nociceptors and peptidergic, mainly thermal nociceptors based on the binding of isolectin B 4 (IB4) and the expression of calcitonin gene-related peptide (CGRP), respectively (SI Appendix, Fig.…”

Section: Mutant Mechanoreceptors and Proprioceptors Are Equally Affecmentioning

confidence: 99%

Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations

Sleigh

Dawes

West

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

135

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Charcot-Marie-Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS. The mechanisms underlying selective nerve pathology in CMT2D remain unresolved, as does the cause of the mild-to-moderate sensory involvement that distinguishes CMT2D from the allelic disorder distal spinal muscular atrophy type V. To elucidate the mechanism responsible for the underlying afferent nerve pathology, we examined the sensory nervous system of CMT2D mice. We show that the equilibrium between functional subtypes of sensory neuron in dorsal root ganglia is distorted by Gars mutations, leading to sensory defects in peripheral tissues and correlating with overall disease severity. CMT2D mice display changes in sensory behavior concordant with the afferent imbalance, which is present at birth and nonprogressive, indicating that sensory neuron identity is prenatally perturbed and that a critical developmental insult is key to the afferent pathology. Through in vitro experiments, mutant, but not wild-type, GlyRS was shown to aberrantly interact with the Trk receptors and cause misactivation of Trk signaling, which is essential for sensory neuron differentiation and development. Together, this work suggests that both neurodevelopmental and neurodegenerative mechanisms contribute to CMT2D pathogenesis, and thus has profound implications for the timing of future therapeutic treatments.aminoacyl-tRNA synthetase | Charcot-Marie-Tooth disease | distal spinal muscular atrophy type V | neuromuscular disease | neurodevelopment C harcot-Marie-Tooth disease (CMT) is a group of genetically diverse peripheral neuropathies that share the main pathological feature of progressive motor and sensory degeneration (1). Although lifespan is usually unaffected, patients display characteristic muscle weakness and wasting predominantly in the extremities, leading to difficulty walking, foot deformities, and reduced dexterity (2). CMT is traditionally divided into type 1/ demyelinating CMTs that display loss of peripheral nerve myelin causing reduced nerve conduction velocity (NCV), type 2/axonal CMTs typified by axon loss with relatively normal NCVs, and intermediate CMTs that share clinical features of CMT1 and -2 (1). Over 80 different genetic loci have been linked to CMT, which is known to affect ∼1/2,500 people, making it the most common group of hereditary neuromuscular disorders (3).Dominant mutations in the glycyl-tRNA synthetase (GlyRS) gene, GARS, are causative of CMT type 2D (CMT2D) [Online Mendelian Inheritance in Man (OMIM) 601472], which normally manifests during adolescence and presents with muscle weakness in the extremities (4). The 2D subtype is one of a number of CMTs associated with mutation of an aminoacyl-tRNA synthetase (ARS) gene (5-8). Humans possess 37 ARS proteins, which covalently link amino acids to their partner transfer RNAs (tRNAs), thereby charging and priming the tRNAs for protein synthesis.This housekeeping function of gl...

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Etv1 Inactivation Reveals Proprioceptor Subclasses that Reflect the Level of NT3 Expression in Muscle Targets

Cited by 105 publications

References 60 publications

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Making sense out of spinal cord somatosensory development

Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations

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