scholarly journals Gli1 regulates the postnatal acquisition of peripheral nerve architecture

2021 ◽  
Author(s):  
Brendan Zotter ◽  
Or Dagan ◽  
Jacob Brady ◽  
Hasna Baloui ◽  
Jayshree Samanta ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Hedgehog Signaling ◽  
Target Cells ◽  
Gli1 Expression ◽  
Desert Hedgehog ◽  
Matrix Production ◽  
Endoneurial Cells ◽  
Cellular Compartments

ABSTRACTPeripheral nerves are organized into discrete cellular compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium - a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a peripheral neuropathy with similar defects. Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs non-canonically i.e., independent of hedgehog signaling. Gli1 and Dhh also have non-redundant activities. In contrast to Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, non-autonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves.SIGNIFICANCE STATEMENTPeripheral nerves are organized into distinct cellular/ECM compartments: the epineurium, perineurium and endoneurium. This organization, with its associated cellular constituents, are critical for the structural and metabolic support of nerves and their response to injury. Here, we show Gli1 - a transcription factor normally expressed downstream of hedgehog signaling - is required for the proper organization of the endoneurium but not the perineurium. Unexpectedly, Gli1 expression by endoneurial cells is independent of, and functions non-redundantly with, Schwann Cell-derived Desert Hedgehog in regulating peripheral nerve architecture. These results further delineate how peripheral nerves acquire their distinctive organization during normal development and highlight mechanisms that may regulate their reorganization in pathologic settings including peripheral neuropathies and nerve injury.

scholarly journals Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

2020 ◽  
Vol 21 (23) ◽  
pp. 9115
Author(s):  
Nathan Moreau ◽  
Yves Boucher
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Hedgehog Signaling ◽  
Future Research ◽  
Chronic Neuropathic Pain ◽  
Desert Hedgehog ◽  
Numerous Cell

The peripheral nervous system has important regenerative capacities that regulate and restore peripheral nerve homeostasis. Following peripheral nerve injury, the nerve undergoes a highly regulated degeneration and regeneration process called Wallerian degeneration, where numerous cell populations interact to allow proper nerve healing. Recent studies have evidenced the prominent role of morphogenetic Hedgehog signaling pathway and its main effectors, Sonic Hedgehog (SHH) and Desert Hedgehog (DHH) in the regenerative drive following nerve injury. Furthermore, dysfunctional regeneration and/or dysfunctional Hedgehog signaling participate in the development of chronic neuropathic pain that sometimes accompanies nerve healing in the clinical context. Understanding the implications of this key signaling pathway could provide exciting new perspectives for future research on peripheral nerve healing.

Hedgehog Signaling in Development and Homeostasis of the Gastrointestinal Tract

2007 ◽  
Vol 87 (4) ◽  
pp. 1343-1375 ◽  
Author(s):  
Gijs R. van den Brink
Keyword(s):  
Gastrointestinal Tract ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Biliary Duct ◽  
Novel Therapy ◽  
Downstream Signaling ◽  
Pancreatic Cancers ◽  
Desert Hedgehog ◽  
Adult Organism

The Hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. In this review I discuss the role of Hedgehog signaling in the development, postnatal maintenance, and carcinogenesis of the gastrointestinal tract. Three mammalian hedgehog genes, sonic hedgehog (Shh), indian hedgehog (Ihh), and desert hedgehog (Dhh) have been identified. Shh and Ihh are important endodermal signals in the endodermal-mesodermal cross-talk that patterns the developing gut tube along different axes. Mutations in Shh, Ihh, and downstream signaling molecules lead to a variety of gross malformations of the murine gastrointestinal tract including esophageal atresia, tracheoesophageal fistula, annular pancreas, midgut malrotation, and duodenal and anal atresia. These congenital malformations are also found in varying constellations in humans, suggesting a possible role for defective Hedgehog signaling in these patients. In the adult, Hedgehog signaling regulates homeostasis in several endoderm-derived epithelia, for example, the stomach, intestine, and pancreas. Finally, growth of carcinomas of the proximal gastrointestinal tract such as esophageal, gastric, biliary duct, and pancreatic cancers may depend on Hedgehog signaling offering a potential avenue for novel therapy for these aggressive cancers.

scholarly journals Epithelial WNT2B and Desert Hedgehog are necessary for human colonoid regeneration after bacterial cytotoxin injury

2018 ◽  
Author(s):  
Julie G. In ◽  
Jianyi Yin ◽  
Michele Doucet ◽  
Robert N. Cole ◽  
Lauren DeVine ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
E Coli ◽  
Stem Cell Proliferation ◽  
Epithelial Regeneration ◽  
Desert Hedgehog ◽  
Crypt Hyperplasia

SUMMARYIntestinal regeneration and crypt hyperplasia after radiation or pathogen injury relies on Wnt signaling to stimulate stem cell proliferation. Mesenchymal Wnts are essential for homeostasis and regeneration in mice, but the role of epithelial Wnts remains largely uncharacterized. Using the enterohemorrhagicE. colisecreted cytotoxin, EspP to induce injury to human colonoids, we evaluated a simplified, epithelial regeneration model that lacks mesenchymal Wnts. Here, we demonstrate that epithelial-produced WNT2B is upregulated following injury and essential for regeneration. Hedgehog signaling, specifically activation via the ligand Desert Hedgehog (DHH), but not Indian or Sonic Hedgehog, is another driver of regeneration and modulates WNT2B expression. These findings highlight the importance of epithelial WNT2B and DHH in regulating human colonic regeneration after injury.

Evidences for a role of nitric oxide in iron homeostasis in plants

2020 ◽  
Author(s):  
Rajesh Kumar Tewari ◽  
Nele Horemans ◽  
Masami Watanabe
Keyword(s):  
Nitric Oxide ◽  
Iron Homeostasis ◽  
Air Pollutant ◽  
Target Cells ◽  
Antioxidant Defence ◽  
Metabolic Functions ◽  
Essential Nutrient ◽  
Fe Homeostasis ◽  
Cellular Compartments

Abstract Nitric oxide (NO) once regarded as a poisonous air pollutant, is now appreciated as a regulatory molecule essential for several biological functions in plants. In this review we not only summarize NO generation in different plant organs and cellular compartments, we also discuss the role of NO in Fe homeostasis particularly in Fe-deficient plants. Fe is one of the most limiting essential nutrient element for plants. Plants often exhibit Fe deficiency symptoms despite of sufficient tissue Fe concentration. NO appears to be not only upregulating Fe uptake mechanisms but it also makes it more bioavailable for metabolic functions. NO forms complexes with Fe which can then be delivered into target cells/ tissues. NO generated in plants can alleviate oxidative stress by regulating antioxidant defence processes probably by improving functional Fe status and by inducing post-translational modifications in the enzymes/proteins involved in the antioxidant defence responses. It is hypothesized that NO acts in cooperation with transcription factors such as bHLH, FIT and IRO (Iron-transcription factor) to regulate expression of enzymes and proteins essential for Fe homeostasis. However, further investigations are needed to unentangle the interaction of NO with the intracellular target molecules which lead to an enhanced internal Fe availability in plants.

scholarly journals Peripheral Nerve Imaging

2021 ◽  
pp. 259-268
Author(s):  
James F. Griffith ◽  
Roman Guggenberger
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Nerve Entrapment ◽  
Nerve Imaging ◽  
Peripheral Nerve Imaging

AbstractThis chapter reviews the basics and practicalities of imaging the peripheral nerves with ultrasound and MRI. Nerve entrapment, tumours, trauma, and inflammation are covered. The complimentary role of ultrasound and MRI in imaging peripheral nerve disorders is stressed.

Role of Peripheral Nerve-Derived Fibroblasts and Schwann Cells in CD40/CD40L and CD80/CD86-Mediated Rejection

2006 ◽  
Vol 22 (06) ◽  
Author(s):  
Deborah Yu ◽  
Sherri Wood ◽  
Keri Smith ◽  
Keith Bishop ◽  
Paul Cederna
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells

STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S279-S294 ◽  
Author(s):  
Paul Robel
Keyword(s):  
Steroid Hormone ◽  
Physiological Activity ◽  
Physiological State ◽  
Target Cells ◽  
Target Tissue ◽  
Hormone Metabolism ◽  
Metabolizing Enzymes ◽  
Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

Individual mechanisms underlying peripheral nerve damage when exposed to metallic mercury

2020 ◽  
Vol 60 (12) ◽  
pp. 918-924
Author(s):  
Dina V. Rusanova ◽  
Oleg L. Lakhman ◽  
Galina M. Bodienkova ◽  
Irina V. Kudaeva ◽  
Natalya G. Kuptsova
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Blood Circulation ◽  
The State ◽  
Contact Period ◽  
Peripheral Nerve Damage ◽  
Demyelinating Disorders ◽  
Peripheral Blood Circulation ◽  
Antibodies To Dna

Introduction. There is a lack of knowledge of the pathophysiological mechanisms that form peripheral nerve disorders in mercury lesions of professional origin. The study aims to reveal the mechanisms underlying peripheral nerve damage in the long-term post-contact period of chronic mercury intoxication (CMI). Materials and methods. Fifty-one people had the diagnosis of a long-term period of CMI. The post-contact period was 8.5±2.6 years. The authors compared the results with a control group of 26 healthy men who had no contact with toxic substances. Stimulating electroneuromyography was performed. We studied the body systems that could contribute to the formation of disorders in the peripheral nerves. Changes in peripheral hemodynamics were studied using reovasography. The content of autoantibodies, neuron-specific enolase, serotonin, histamine, catecholamines (epinephrine, dopamine), metanephrine, and neurotrophin-3 was reviewed. The content of ceruloplasmin, secondary products of lipid peroxidation processes, reduced glutathione, the activity of superoxide dismutase and the content of nitric oxide levels were determined. Results. The study established pathogenetic structural links of peripheral nerve disorders. The autoimmune process's role was to increase the range of antibodies to the MAG protein and increase the level of antibodies to DNA. Violations of elastic-tonic properties of peripheral vessels could be associated with the functional state of motor axons. The increased content of neurotransmitters is related to the state of peripheral blood circulation; the most pronounced changes were on the legs, which could contribute to the occurrence and maintenance of vasoconstriction. The role of oxidative stress in the formation of demyelinating disorders in patients' peripheral nerves in the long-term period of CRI is possible. Conclusion. Neuroimmunological processes has an essential role in the development of peripheral nerve demyelination was shown, which consists in an increase in the content of antibodies to the MAG protein expressed on Schwann cells of peripheral nerves and in an increase in the level of antibodies to DNA involved in the formation of demyelinating changes when exposed to metallic mercury. The revealed pathological changes in the state of the peripheral blood circulation, characterized by a violation of the vessels' elastic-tonic properties, leading to demyelination of motor axons in patients in the long-term period of CMI. The increased content of neurotransmitters in the examined is of great importance in the state of peripheral circulation. Pronounced changes in blood circulation are established on the lower extremities, which may be associated with the predominance of α-adrenergic receptors in the arterial bed and may contribute to the occurrence and maintenance of vasoconstriction in the legs. The relationship between changes in indicators of oxidative stress, consisting of a decrease in the value of superoxide dismutase and reduced glutathione, and the formation of demyelinating disorders of peripheral nerves in patients in the long-term period of CMI has been proved.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

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