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.

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 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 Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Alison M. Hixon ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Sialic Acid ◽  
Motor Neuron ◽  
Axonal Transport ◽  
Motor Neurons ◽  
The United States ◽  
Retrograde Axonal Transport ◽  
Spinal Motor Neurons ◽  
Acute Flaccid Myelitis ◽  
Spinal Motor ◽  
Enterovirus D68

ABSTRACTEnterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons.IMPORTANCEEnterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

scholarly journals A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily.

1994 ◽  
Vol 14 (10) ◽  
pp. 7025-7035 ◽  
Author(s):  
R Apfel ◽  
D Benbrook ◽  
E Lernhardt ◽  
M A Ortiz ◽  
G Salbert ◽  
...  
Keyword(s):  
Amino Acid ◽  
Thyroid Hormone ◽  
Dna Binding ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Dna Sequences ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Orphan Receptor ◽  
Retinoid Receptor

The steroid/hormone nuclear receptor superfamily comprises several subfamilies of receptors that interact with overlapping DNA sequences and/or related ligands. The thyroid/retinoid hormone receptor subfamily has recently attracted much interest because of the complex network of its receptor interactions. The retinoid X receptors (RXRs), for instance, play a very central role in this subfamily, forming heterodimers with several receptors. Here we describe a novel member of this subfamily that interacts with RXR. Using a v-erbA probe, we obtained a cDNA which encodes a novel 445-amino-acid protein, RLD-1, that contains the characteristic domains of nuclear receptors. Northern (RNA) blot analysis showed that in mature rats, the receptor is highly expressed in spleen, pituitary, lung, liver, and fat. In addition, weaker expression is observed in several other tissues. Amino acid sequence alignment and DNA-binding data revealed that the DNA-binding domain of the new receptor is related to that of the thyroid/retinoid subgroup of nuclear receptors. RLD-1 preferentially binds as a heterodimer with RXR to a direct repeat of the half-site sequence 5'-G/AGGTCA-3', separated by four nucleotides (DR-4). Surprisingly, this binding is dependent to a high degree on the nature of the spacing nucleotides. None of the known nuclear receptor ligands activated RLD-1. In contrast, a DR-4-dependent constitutive transcriptional activation of a chloramphenicol acetyltransferase reporter gene by the RLD-1/RXR alpha heterodimer was observed. Our data suggest a highly specific role for this novel receptor within the network of gene regulation by the thyroid/retinoid receptor subfamily.

Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling

2010 ◽  
Vol 222 (2) ◽  
pp. 347-356 ◽  
Author(s):  
Ya-Hui Huang ◽  
Chen-Hsin Liao ◽  
Ruey-Nan Chen ◽  
Chia-Jung Liao ◽  
Kwang-Huei Lin
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Orphan Receptor ◽  
Receptor Signaling

scholarly journals The manipulation of spinal motor neuron axonal growth promotes spinal cord repair

2021 ◽  
Author(s):  
Feng Wang ◽  
Xinya Fu ◽  
Meiemei Li ◽  
Xingran Wang ◽  
Jile Xie ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Axonal Regeneration ◽  
Axonal Growth ◽  
Treatment Method ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Cord Injury ◽  
Spinal Cord Repair

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.

Restricted expression of mutant SOD1 in spinal motor neurons and interneurons induces motor neuron pathology

2008 ◽  
Vol 29 (3) ◽  
pp. 400-408 ◽  
Author(s):  
Lijun Wang ◽  
Kamal Sharma ◽  
Han-Xiang Deng ◽  
Teepu Siddique ◽  
Gabriella Grisotti ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Mutant Sod1 ◽  
Spinal Motor Neurons ◽  
Spinal Motor

scholarly journals The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor

2003 ◽  
Vol 23 (15) ◽  
pp. 5122-5131 ◽  
Author(s):  
Takahiro Ishizuka ◽  
Mitchell A. Lazar
Keyword(s):  
Thyroid Hormone ◽  
Histone Deacetylase ◽  
Hormone Receptor ◽  
Transcriptional Repression ◽  
Thyroid Hormone Receptor ◽  
Histone Deacetylation ◽  
Orphan Receptor ◽  
Small Interfering Rnas ◽  
Histone Deacetylase 3 ◽  
Nonspecific Effects

ABSTRACT Nuclear receptor corepressors (N-CoR) and silencing mediator for retinoid and thyroid receptors (SMRT) have both been implicated in thyroid hormone receptor (TR)-mediated repression. Here we show that endogenous N-CoR, TBL1, and histone deacetylase 3 (HDAC3), but not HDAC1, -2, or -4, are recruited to a stably integrated reporter gene repressed by unliganded TR as well as the orphan receptor RevErb. Unliganded TR also recruits this complex to a transiently transfected reporter, and transcriptional repression is associated with local histone deacetylation that is reversed by the presence of thyroid hormone. Knockdown of N-CoR using small interfering RNAs markedly reduces repression by the TR ligand binding domain in human 293T cells, whereas knockdown of SMRT has little effect. RevErb repression appears to involve both corepressors in this system. Knockdown of HDAC3 markedly reduces repression by both TR and RevErb, while knockdown of HDAC1 or 2 has more modest, partly nonspecific effects. Thus, HDAC3 is critical for repression by multiple nuclear receptors and the N-CoR HDAC3 complex plays a unique and necessary role in TR-mediated gene repression in human 293T cells.

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