Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1001940 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25510000.fastq.gz | Fastqsanger.gz | |||
| SRR25510001.fastq.gz | Fastqsanger.gz | |||
| SRR25510002.fastq.gz | Fastqsanger.gz | |||
| SRR25510003.fastq.gz | Fastqsanger.gz | |||
| SRR25510004.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 64 |
Similar Datasets
Project description:Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally-distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes, and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily-conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.
2023-08-24 | GSE240026 | GEO
Project description:The flexibility of motor actions is ingrained in the diversity of neurons and how they are organized into functional circuit modules, yet our knowledge of the molecular underpinning of motor circuit modularity remains limited. Locomotion is a motor behavior characterized by sudden changes in speed and strength enabled by the coordinated recruitment of different motoneuron subtypes. Here we use adult zebrafish to link the molecular diversity of motoneurons and the rhythm-generating V2a interneurons with their modular circuit organization that is responsible for changes in locomotor speed. We show that the molecular diversity of motoneurons and V2a interneurons reflects their functional segregation into slow, intermediate or fast subtypes. Furthermore, we reveal shared molecular signatures between V2a interneurons and motoneurons of the three speed circuit modules. Overall, by characterizing how the molecular diversity of motoneurons and V2a interneurons relates to their function, connectivity and behavior, our study provides important insights not only into the molecular mechanisms for neuronal and circuit diversity for locomotor flexibility but also for charting circuits for motor actions in general.
2023-09-29 | GSE243993 | GEO
Project description:Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.
| S-EPMC10600875 | biostudies-literature
Project description:Molecular blueprints for spinal circuit modules controlling locomotor speed
| PRJNA1020854 | ENA
Project description:Generation of autologous motor neurons holds a great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows the generation of target cell types from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic populations that are not readily scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequential induction of OCT4 and LHX3. Our strategy enables large production of pure iMNs through self-renewing iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited the hallmarks of spinal motor neurons including cellular morphology, marker expression, electrophysiological property, synaptic activity, and formation of neuromuscular junctions. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in SCI model. Taken together, our advanced strategy will provide tools to acquire sufficient iMNs that may represent a promising cell source for personalized cell therapy.
2020-06-29 | GSE149664 | GEO
Project description:A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment
| PRJNA784972 | ENA
Project description:The functions of the Hsp70 genes were studied using a line of D. melanogaster with knockout of six these genes out of thirteen. Namely, effect of knockout of Hsp70 genes on negative geotaxis climbing (locomotor) speed and the ability to adapt to climbing training (0.5-1.5 h/day, 7 days/week, 19 days) were examined. Seven- and 23-day-old Hsp70– flies demonstrated a comparable reduction (2-fold) in locomotor speed and widespread changes in leg skeletal muscle transcriptome (RNA-seq), compared to w1118 flies. To identify the functions of genes related to decreased locomotor speed the overlapped differentially expressed genes at both time points were analyzed: the up-regulated genes encoded extracellular proteins, regulators of drug metabolism and antioxidant response, while down-regulated genes encoded regulators of carbohydrate metabolism and transmembrane proteins. Additionally, in Hsp70– flies, activation of transcription factors related to disruption of the fibril structure and heat shock response (Hsf) were predicted, using the position weight matrix approach. In the control flies, adaptation to chronic exercise training was associated mainly with gene response to a single exercise bout, while the predicted transcription factors were related to stress/immune (Hsf, NF-kB, etc.) and early gene response. In contrast, Hsp70– flies demonstrated no adaptation to training, as well as significantly impaired gene response to a single exercise bout. In conclusion, the knockout of Hsp70 genes not only reduced physical performance, but also disrupted adaptation to chronic physical training, which is associated with changes in leg skeletal muscle transcriptome and impaired gene response to a single exercise bout.
2023-08-01 | GSE239395 | GEO
Project description:Generation of induced motor neurons (iMNs) from human fibroblasts facilitates locomotor recovery after spinal cord injury
| PRJNA629571 | ENA
Project description:Introduction: Male estrogen receptor beta (ERβ) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration and reduced GABAergic signaling. Effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ERβ loss have not been investigated. Objective: The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. Methods: Locomotor activity of WT and BERKO male mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA-sequencing, electron microscopy, electrophysiology, and immunofluorescence techniques. In addition, we established oligodendrocyte cultures from WT and BERKO mouse embryonic stem cells to evaluate oligodendrocyte function. Results: Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission, as well as a defective oligodendrocyte differentiation accompanied by myelin defects. The effects of loss of ERβ on oligodendrocyte differentiation was confirmed in vitro. Conclusion: ERβ is an important regulator of GABAergic interneurons and oligodendrocyte differentiation, which impacts on adult M1 cortex function, and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.
2019-12-01 | GSE139428 | GEO
Project description:The fidelity of motor control requires the precise positional arrangement of motor pools and the establishment of synaptic connections between these pools. In the developing spinal cord, motor nerves project to specific target muscles and receive proprioceptive input from the muscles via the sensorimotor circuit. LIM-homeodomain transcription factors are known to successively restrict specific motor neuronal fates during neural development; however, it remains unclear to what extent they contribute to limb-based motor pools and locomotor circuits. Here, we showed in mice that deletion of Isl2 resulted in scattered motor pools, primarily in the median motor column and lateral LMC (LMCl) populations, and lacked Pea3 expression in the hindlimb motor pools, accompanied by reduced terminal axon branching and disorganized neuromuscular junctions. Transcriptomic analysis of Isl2-deficient spinal cords revealed that a variety of genes involved in motor neuron differentiation, axon development, and synapse organization were downregulated in hindlimb motor pools. Moreover, the loss of Isl2 impaired sensorimotor connectivity and hindlimb locomotion. Together, our studies indicate that Isl2 plays a critical role in organizing motor pool position and sensorimotor circuits in hindlimb motor pools.
2023-11-01 | GSE217297 | GEO