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Recently, we showed that Schwann cells transfer ribosomes to injured axons. Here, we demonstrate that Schwann cells transfer ribosomes to regenerating axons in vivo. For this, we used lentiviral vector‐mediated expression of ribosomal protein L4 and eGFP to label ribosomes in Schwann cells. Two approaches were followed. First, we transduced Schwann cells in vivo in the distal trunk of the sciatic...
Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life, however, it remains unclear how OECs respond to a major injury. We have examined the proliferation and migration of OECs following unilateral bulbectomy in postnatal mice. S100ß‐DsRed and OMP‐ZsGreen transgenic mice were used to visualize OECs and olfactory neurons, respectively, and we used the...
Missense mutations affecting the LITAF gene (also known as SIMPLE) lead to the dominantly inherited peripheral neuropathy Charcot‐Marie‐Tooth disease type 1C (CMT1C). In this study, we sought to determine the requirement of Litaf function in peripheral nerves, the only known affected tissue in CMT1C. We reasoned that this knowledge is a prerequisite for a thorough understanding of the underlying disease...
Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation...
The medicinal leech is notable for its capacity to regenerate its central nervous system (CNS) following mechanical trauma. Using an electrochemical nitric oxide (NO)‐selective electrode to measure NO levels, we found that the time course of NO release in the injured leech CNS is partially under the control of endocannabinoids, namely, N‐arachidonyl ethanolamide (AEA) and 2‐arachidonyl glycerol (2‐AG)...
In contrast to mammals, the spinal cord of lampreys spontaneously recovers from a complete spinal cord injury (SCI). Understanding the differences between lampreys and mammals in their response to SCI could provide valuable information to propose new therapies. Unique properties of the astrocytes of lampreys probably contribute to the success of spinal cord regeneration. The main aim of our study...
In retinas where Müller glia have been stimulated to become progenitor cells, reactive microglia are always present. Thus, we investigated how the activation or ablation of microglia/macrophage influences the formation of Müller glia‐derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of the Interleukin‐6 (IL6) stimulated the reactivity of microglia/macrophage, whereas other...
Olfactory ensheathing cells (OECs) support the ability of the olfactory neuraxis to continually retarget within the mature central nervous system. This has led many groups to transplant OECS into the lesioned rodent spinal cord (SCd) in vivo, with variable degrees of anatomical, physiological, and behavioral success. Some of the most conflicting results in OEC transplantation have come from the corticospinal...
Microglia are rapidly activated in the central nervous system (CNS) in response to a variety of injuries, including inflammation, trauma, and stroke. In addition to modulation of the innate immune response, a key function of microglia is the phagocytosis of dying cells and cellular debris, which can facilitate recovery. Despite emerging evidence that axonal debris can pose a barrier to regeneration...
The study of factors that regulate the survival, proliferation, and differentiation of neural precursor cells (NPCs) is essential to understand neural development as well as brain regeneration. The Nuclear Factor of Activated T Cells (NFAT) is a family of transcription factors that can affect these processes besides playing key roles during development, such as stimulating axonal growth in neurons,...
The straightforward concept that accentuated Wnt signaling via the Wnt‐receptor‐β‐catenin‐TCF/LEF cascade (also termed canonical Wnt signaling or Wnt/β‐catenin signaling) delays or blocks oligodendrocyte differentiation is very appealing. According to this concept, canonical Wnt signaling is responsible for remyelination failure in multiple sclerosis and for persistent hypomyelination in periventricular...
Reactive gliosis is an umbrella term for various glia functions in neurodegenerative diseases and upon injury. Specifically, Müller glia (MG) in some species readily regenerate retinal neurons to restore vision loss after insult, whereas mammalian MG respond by reactive gliosis—a heterogeneous response which frequently includes cell hypertrophy and proliferation. Limited regeneration has been stimulated...
A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self‐repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have...
Müller glia‐derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell‐signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8‐ and TGFβ/Smad2/3‐signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8...
Microglia are the resident tissue macrophages of the central nervous system including the retina. Under pathophysiological conditions, microglia can signal to Müller cells, the major glial component of the retina, affecting their morphological, molecular, and functional responses. Microglia–Müller cell interactions appear to be bidirectional shaping the overall injury response in the retina. Hence,...
Membrane metallo‐endopeptidase (MME), also known as neprilysin (NEP), has been of interest for its role in neurodegeneration and pain due to its ability to degrade β‐amyloid and substance‐P, respectively. In addition to its role in the central nervous system, MME has been reported to be expressed in the peripheral system, specifically in the inner and outer border of myelinating fibers, in the Schmidt‐Lantermann...
Upon retina injury, Müller glia in the zebrafish retina respond by generating multipotent progenitors to repair the retina. However, the complete mechanisms underlying retina regeneration remain elusive. Here we report inflammation‐induced mammalian target of rapamycin (mTOR) signaling in the Müller glia is essential for retina regeneration in adult zebrafish. We show after a stab injury, mTOR is...
Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion...
Damage to the zebrafish retina stimulates resident Müller glia to reprogram, reenter the cell cycle, divide asymmetrically, and produce neuronal progenitor cells that amplify and differentiate into the lost neurons. The transition from quiescent to proliferative Müller glia involves both positive and negative regulators. We previously demonstrated that the Notch signaling pathway represses retinal...
Hirschsprung disease (HSCR) is characterized by congenital absence of enteric neurons in distal portions of the gut. Although recent studies identified Schwann cell precursors (SCPs) as a novel cellular source of enteric neurons, it is unknown how SCPs contribute to the disease phenotype of HSCR. Using Schwann cell‐specific genetic labeling, we investigated SCP‐derived neurogenesis in two mouse models...
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