scholarly journals HoxD transcription factors define monosynaptic sensory-motor specificity in the developing spinal cord

Development ◽  
2021 ◽  
Author(s):  
Fumiyasu Imai ◽  
Mike Adam ◽  
S. Steven Potter ◽  
Yutaka Yoshida
Keyword(s):  
Spinal Cord ◽  
Transcription Factors ◽  
Motor Neuron ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Critical Role ◽  
Dendrite Morphology ◽  
Sensory Motor ◽  
Integral Role ◽  
Developing Spinal Cord

The specificity of monosynaptic connections between proprioceptive sensory neurons and their recipient spinal motor neurons depends on multiple factors, including motor neuron positioning and dendrite morphology, axon projection patterns of proprioceptive sensory neurons in the spinal cord, and the ligand-receptor molecules involved in cell-to-cell recognition. However, with few exceptions, the transcription factors engaged in this process are poorly characterized. We show here, that members of the HoxD family of transcription factors play a critical role in the specificity of monosynaptic sensory-motor connections. Mice lacking Hoxd9, Hoxd10, and Hoxd11 exhibit defects in locomotion but have no obvious defects in motor neuron positioning or dendrite morphology through the medio-lateral and rostro-caudal axes. However, we found that quadriceps motor neurons in these mice show aberrant axon development and receive inappropriate inputs from proprioceptive sensory axons innervating the obturator muscle. These genetic studies demonstrate that the HoxD transcription factors play an integral role in the synaptic specificity of monosynaptic sensory-motor connections in the developing spinal cord.

The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 969-982 ◽  
Author(s):  
M. Ensini ◽  
T.N. Tsuchida ◽  
H.G. Belting ◽  
T.M. Jessell
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Tube ◽  
Motor Behavior ◽  
Neural Tube Closure ◽  
Paraxial Mesoderm ◽  
Homeodomain Protein ◽  
Mesodermal Cell ◽  
Developing Spinal Cord

The generation of distinct classes of motor neurons is an early step in the control of vertebrate motor behavior. To study the interactions that control the generation of motor neuron subclasses in the developing avian spinal cord we performed in vivo grafting studies in which either the neural tube or flanking mesoderm were displaced between thoracic and brachial levels. The positional identity of neural tube cells and motor neuron subtype identity was assessed by Hox and LIM homeodomain protein expression. Our results show that the rostrocaudal identity of neural cells is plastic at the time of neural tube closure and is sensitive to positionally restricted signals from the paraxial mesoderm. Such paraxial mesodermal signals appear to control the rostrocaudal identity of neural tube cells and the columnar subtype identity of motor neurons. These results suggest that the generation of motor neuron subtypes in the developing spinal cord involves the integration of distinct rostrocaudal and dorsoventral patterning signals that derive, respectively, from paraxial and axial mesodermal cell groups.

Lower Motor Neuron Disease with Accumulation of Neurofilaments in a Cat

1976 ◽  
Vol 13 (6) ◽  
pp. 428-435 ◽  
Author(s):  
M. Vandevelde ◽  
C. E. Greene ◽  
E. J. Hoff
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Histological Examination ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Nerve Cells ◽  
Lower Motor Neuron ◽  
Motor Neuron Diseases ◽  
Lower Motor Neuron Disease

A young cat had signs of tetraparesis that progressed to tetraplegia within a few weeks. Clinically, there was lower motor neuron disease with areflexia and muscle atrophy in all limbs. Degeneration of the motor neurons in the spinal cord was seen on histological examination. Ultrastructurally, the degeneration of nerve cells was characterized by abnormal proliferation of neurofilaments. These findings were compared to other motor neuron diseases and neurofibrillary accumulations in man and animals.

scholarly journals A Comprehensive Profile of ChIP-Seq-Based Olig2 Target Genes in Motor Neuron Progenitor Cells Suggests the Possible Involvement of Olig2 in the Pathogenesis of Amyotrophic Lateral Sclerosis

2015 ◽  
Vol 7 ◽  
pp. JCNSD.S23210 ◽  
Author(s):  
Jun-Ichi Satoh ◽  
Naohiro Asahina ◽  
Shouta Kitano ◽  
Yoshihiro Kino
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Progenitor Cells ◽  
Motor Neurons ◽  
Target Genes ◽  
Molecular Networks ◽  
Bhlh Transcription Factor ◽  
Wide Range ◽  
Lateral Sclerosis

Background Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease that primarily affects motor neurons in the cerebral cortex and the spinal cord. Recent evidence indicates that dysfunction of oligodendrocytes is implicated in the pathogenesis of ALS. The basic helix–loop–helix (bHLH) transcription factor Olig2 plays a pivotal role in the development of both motor neurons and oligodendrocytes in the progenitor of motor neuron (pMN) domain of the spinal cord, supporting evidence for the shared motor neuron/oligodendrocyte lineage. However, a comprehensive profile of Olig2 target genes in pMNs and oligodendrocyte progenitor cells (OPCs) with relevance to the pathogenesis of ALS remains to be characterized. Methods By analyzing the ChIP-Seq datasets numbered SRP007566 and SRP015333 with the Strand NGS program, we identified genome-wide Olig2 target genes in pMNs and OPCs, followed by molecular network analysis using three distinct bioinformatics tools. Results We identified 5966 Olig2 target genes in pMNs, including Nkx2.2, Pax6, Irx3, Ngn2, Zep2 (Cip1), Trp3, Mnx1 (Hb9), and Cdkn1a, and 1553 genes in OPCs. The genes closely related to the keyword “alternative splicing” were enriched in the set of 740 targets overlapping between pMNs and OPCs. Furthermore, approximately one-third of downregulated genes in purified motor neurons of presymptomatic mutant SOD1 transgenic mice and in lumbar spinal cord tissues of ALS patients corresponded to Olig2 target genes in pMNs. Molecular networks of Olig2 target genes indicate that Olig2 regulates a wide range of genes essential for diverse neuronal and glial functions. Conclusions These observations lead to a hypothesis that aberrant regulation of Olig2 function, by affecting biology of both motor neurons and oligodendrocytes, might be involved in the pathogenesis of ALS.

scholarly journals Groucho/TLE opposes axial to hypaxial motor neuron development

2020 ◽  
Author(s):  
Adèle Salin-Cantegrel ◽  
Rola Dali ◽  
Jae Woong Wang ◽  
Marielle Beaulieu ◽  
Mira Deshmukh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
List Type ◽  
Neuron Development ◽  
In Ovo ◽  
Motor Circuits ◽  
Axial Muscles ◽  
Muscle Innervation

ABSTRACTSpinal cord motor neuron diversity and the ensuing variety of motor circuits allow for the processing of elaborate muscular behaviours such as body posture and breathing. Little is known, however, about the molecular mechanisms behind the specification of axial and hypaxial motor neurons controlling postural and respiratory functions respectively. Here we show that the Groucho/TLE (TLE) transcriptional corepressor is a multi-step regulator of axial and hypaxial motor neuron diversification in the developing spinal cord. TLE first promotes axial motor neuron specification at the expense of hypaxial identity by cooperating with non-canonical WNT5A signalling within the motor neuron progenitor domain. TLE further acts during post-mitotic motor neuron diversification to promote axial motor neuron topology and axonal connectivity whilst suppressing hypaxial traits. These findings provide evidence for essential and sequential roles of TLE in the spatial and temporal coordination of events regulating the development of motor neurons influencing posture and controlling respiration.HIGHLIGHTSGroucho/TLE mediates non-canonical WNT signalling in developing motor neuronsNon canonical WNT:TLE pathway regulates thoracic motor neuron diversificationTLE promotes axial while inhibiting hypaxial motor neuron developmentTLE influences developing motor neuron topology and muscle innervationIN BRIEFSalin-Cantegrel et al use in ovo engineered approaches to show that a non-canonical WNT:TLE pathway coordinates temporally and spatially separated elements of motor neuron diversification, repressing hypaxial motor neuron development to promote the axial fate.GRAPHICAL ABSTRACTTLE contribution to the development of thoracic somatic motor columnsProgenitor cells in the ventral pMN domain are exposed to higher concentrations of non-canonical WNTs and express more TLE. Cooperation of non-canonical WNTs and TLE renders ventral pMN progenitors refractory to a respiratory MN fate, thereby contributing to the separation of MMC and RMC MN lineages. Differentiating MNs that maintain high TLE expression also maintain LHX3 expression, adopt axial motor neuron topology and connect to axial muscles. TLE activity in differentiating MMC MNs prevents the acquisition of respiratory MN topology and innervation traits.

scholarly journals Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function

2020 ◽  
Author(s):  
Yinan Li ◽  
Anthony Osuma ◽  
Edgar Correa ◽  
Munachiso A. Okebalama ◽  
Pauline Dao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Genome Engineering ◽  
Life Stages ◽  
C Elegans ◽  
Neuronal Identity ◽  
Protein Classes ◽  
Selector Function

ABSTRACTTerminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of C. elegans cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing “temporal modularity” in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g., receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3’s temporal modularity via genome engineering affects locomotion. Another C. elegans terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.

scholarly journals The effect of sonic hedgehog on motor neuron positioning in the spinal cord during chicken embryo development

2017 ◽  
Author(s):  
Ciqing Yang ◽  
Xiaoying Li ◽  
Qiuling Li ◽  
Qiong Li ◽  
Han Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Embryo Development ◽  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Chicken Embryo ◽  
Positional Information ◽  
Underlying Mechanism ◽  
Correct Location ◽  
Information Cell

ABSTRACTSonic hedgehog (Shh) is a vertebrate homologue of the secreted Drosophila protein hedgehog, and is expressed by the notochord and the floor plate in the developing spinal cord. Shh provides signals relevant for positional information, cell proliferation, and possibly cell survival depending on the time and location of the expression. Although the role of Shh in providing positional information in the neural tube has been experimentally proven, the exact underlying mechanism still remains unclear. In this study, we report that overexpression of Shh affects motor neuron positioning in the spinal cord during chicken embryo development by inducing abnormalities in the structure of the motor column and motor neuron integration. In addition, Shh overexpression inhibits the expression of dorsal transcription factors and commissural axon projections. Our results indicate that correct location of Shh expression is the key to the formation of the motor column. In conclusion, the overexpression of Shh in the spinal cord not only affects the positioning of motor neurons, but also induces abnormalities in the structure of the motor column.

scholarly journals “Stretch-Growth” of Motor Axons in Custom Mechanobioreactors to Generate Long-Projecting Axonal and Axonal-Myocyte Constructs

2019 ◽  
Author(s):  
Kritika S. Katiyar ◽  
Laura A. Struzyna ◽  
Suradip Das ◽  
D. Kacy Cullen
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Motor Axon ◽  
Central Feature ◽  
Motor Axons ◽  
Ganglion Neurons

AbstractThe central feature of peripheral motor axons is their remarkable lengths as they project from a motor neuron residing in the spinal cord to an often-distant target muscle. However, to date in vitro models have not replicated this central feature owing to challenges in generating motor axon tracts beyond a few millimeters in length. To address this, we have developed a novel combination of micro-tissue engineering and mechanically assisted growth techniques to create long-projecting centimeter-scale motor axon tracts. Here, primary motor neurons were isolated from the spinal cords of rats and induced to form engineered micro-spheres via forced aggregation in custom micro-wells. This three-dimensional micro-tissue yielded healthy motor neurons projecting dense, fasciculated axonal tracts. Within our custom-built mechanobioreactors, motor neuron culture conditions, neuronal/axonal architecture, and mechanical growth conditions were systematically optimized to generate parameters for robust and efficient “stretch-growth” of motor axons. We found that axons projecting from motor neuron aggregates were able to respond to axon displacement rates at least 10 times greater than that tolerated by axons projecting from dissociated motor neurons. The growth and structural characteristics of these stretch-grown motor axons were compared to benchmark stretch-grown axons from sensory dorsal root ganglion neurons, revealing similar axon densities yet increased motor axon fasciculation. Finally, motor axons were integrated with myocytes and then stretch-grown to create novel long-projecting axonal-myocyte constructs that better recreate characteristic dimensions of native nerve-muscle anatomy. This is the first demonstration of mechanical elongation of spinal cord motor axons and may have applications as anatomically inspired in vitro testbeds or as tissue engineered “living scaffolds” for targeted axon tract reconstruction following nervous system injury or disease.Significance StatementWe have developed novel axon tracts of unprecedented lengths spanning either two discrete populations of neurons or a population of neurons and skeletal myocytes. This is the first demonstration of “stretch-grown” motor axons that recapitulate the structure of spinal motor neurons in vivo by projecting long axons from a pool of motor neurons to distant targets, and may have applications as anatomically inspired in vitro test beds to study mechanisms of axon growth, development, and neuromuscular function in anatomically accurate axo-myo constructs; as well as serve as “living scaffolds” in vivo for targeted axon tract reconstruction following nervous system trauma.

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