Regulation of oligodendrocyte differentiation: a role for retinoic acid in the spinal cord

Development ◽  
1994 ◽  
Vol 120 (3) ◽  
pp. 649-660
Author(s):  
E. Noll ◽  
R.H. Miller
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Embryonic Development ◽  
Ventricular Zone ◽  
Distinct Group ◽  
Oligodendrocyte Differentiation ◽  
Distinct Cell ◽  
Embryonic Spinal Cord ◽  
Oligodendrocyte Precursors

During development, oligodendrocyte precursors undergo sequential stages of differentiation characterized by expression of distinct cell surface properties and proliferative responses. Although both PDGF and bFGF are mitogenic for these cells, the factors that regulate the progression of oligodendrocyte precursors through their differentiative program remain unclear. One factor present in the embryonic spinal cord that may regulate differentiation of oligodendrocyte precursors is retinoic acid. Here we show that retinoic acid inhibits the maturation of embryonic spinal cord oligodendrocyte precursors in vitro at an early, highly motile stage of differentiation, characterized by the expression of A2B5 immunoreactivity. Basic FGF acts both as a mitogen and an inhibitor of spinal cord oligodendrocyte precursor maturation, but at a significantly later stage of differentiation, characterized by the expression of O4 immunoreactivity. In the presence of RA both the mitogenic and differentiation inhibiting effects of bFGF are abolished, consistent with RA acting as an early regulator of oligodendrocyte differentiation. During embryonic development, oligodendrocyte precursors arise initially from a distinct group of cells at the ventral ventricular zone of the spinal cord. Myelination of the entire spinal cord is dependent on the migration of immature precursor cells to peripheral developing white matter. Since the embryonic spinal cord has the capacity to release relatively high levels of retinoids, we propose that RA inhibits oligodendrocyte differentiation during early embryonic development permitting their dispersal throughout the entire spinal cord.

scholarly journals Effects of Electroacupuncture and the Retinoid X Receptor (Rxr) Signalling Pathway on Oligodendrocyte Differentiation in the Demyelinated Spinal Cord of Rats

2017 ◽  
Vol 35 (2) ◽  
pp. 122-132 ◽  
Author(s):  
Xiao-Hua Yang ◽  
Ying Ding ◽  
Wen Li ◽  
Rong-Yi Zhang ◽  
Jin-Lang Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Retinoid X Receptor ◽  
Signalling Pathway ◽  
Control Group ◽  
Oligodendrocyte Differentiation ◽  
Adult Rats ◽  
Group Protein ◽  
Embryonic Spinal Cord ◽  
Oligodendrocyte Precursor

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination.

Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2419-2429 ◽  
Author(s):  
D.M. Orentas ◽  
J.E. Hayes ◽  
K.L. Dyer ◽  
R.H. Miller
Keyword(s):  
Spinal Cord ◽  
Sonic Hedgehog ◽  
Ventricular Zone ◽  
Developmental Period ◽  
Dorsal Spinal Cord ◽  
Shh Signaling ◽  
Oligodendrocyte Precursors ◽  
Dorsal Spinal

Spinal cord oligodendrocyte precursors arise in the ventral ventricular zone as a result of local signals. Ectopic oligodendrocyte precursors can be induced by sonic hedgehog (Shh) in explants of chick dorsal spinal cord over an extended developmental period. The role of Shh during normal oligodendrocyte development is, however, unclear. Here we demonstrate that Shh is localized to the ventral spinal cord immediately prior to, and during the appearance of oligodendrocyte precursors. Continued expression of Shh is required for the appearance of spinal cord oligodendrocyte precursors as neutralization of Shh signaling both in vivo and in vitro during a defined developmental period blocked their emergence. The inhibition of oligodendrocyte precursor emergence in the absence of Shh signaling was not the result of inhibiting precursor cell proliferation, and the neutralization of Shh signaling after the emergence of oligodendrocyte precursors had no effect on the appearance of additional cells or their subsequent differentiation. Similar concentrations of Shh induce motor neurons and oligodendrocytes in dorsal spinal cord explants. However, in explants from early embryos the motor neuron lineage is preferentially expanded while in explants from older embryos the oligodendrocyte lineage is preferentially expanded.

Early development and dispersal of oligodendrocyte precursors in the embryonic chick spinal cord

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1743-1754 ◽  
Author(s):  
K. Ono ◽  
R. Bansal ◽  
J. Payne ◽  
U. Rutishauser ◽  
R.H. Miller
Keyword(s):  
Spinal Cord ◽  
Ventricular Zone ◽  
General Characteristic ◽  
Central Canal ◽  
Vertebrate Development ◽  
Dorsal Spinal Cord ◽  
Oligodendrocyte Precursors ◽  
Dorsal Spinal ◽  
Chick Spinal Cord

Oligodendrocytes, the myelinating cells of the vertebrate CNS, originally develop from cells of the neuroepithelium. Recent studies suggest that spinal cord oligodendrocyte precursors are initially localized in the region of the ventral ventricular zone and subsequently disperse throughout the spinal cord. The characteristics of these early oligodendrocyte precursors and their subsequent migration has been difficult to assay directly in the rodent spinal cord due to a lack of appropriate reagents. In the developing chick spinal cord, we show that oligodendrocyte precursors can be specifically identified by labeling with O4 monoclonal antibody. In contrast to rodent oligodendrocyte precursors, which express O4 immunoreactivity only during the later stages of maturation, in the chick O4 immunoreactivity appears very early and its expression is retained through cellular maturation. In embryos older than stage 35, O4+ cells represent the most immature, self-renewing, cells of the chick spinal cord oligodendrocyte lineage. In the intact chick spinal cord, the earliest O4+ cells are located at the ventral ventricular zone where they actually contribute to the ventricular lining of the central canal. The subsequent migration of O4+ cells into the dorsal region of the spinal cord temporally correlates with the capacity of isolated dorsal spinal cord to generate oligodendrocytes in vitro. Biochemical analysis suggests O4 labels a POA-like antigen on the surface of chick spinal cord oligodendrocyte precursors. These studies provide direct evidence for the ventral ventricular origin of spinal cord oligodendrocytes, and suggest that this focal source of oligodendrocytes is a general characteristic of vertebrate development.

scholarly journals Apoptosis in metanephric development.

1992 ◽  
Vol 119 (5) ◽  
pp. 1327-1333 ◽  
Author(s):  
C Koseki ◽  
D Herzlinger ◽  
Q al-Awqati
Keyword(s):  
Spinal Cord ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Phorbol Esters ◽  
Dna Degradation ◽  
Morphological Evidence ◽  
Metanephric Mesenchyme ◽  
Embryonic Spinal Cord

During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin-D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis. Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelial requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation.

scholarly journals Use of retinoids during oocyte maturation diminishes apoptosis in caprine embryos

2015 ◽  
Vol 63 (2) ◽  
pp. 234-242 ◽  
Author(s):  
Juliana C. Z. Conceição ◽  
Marcelo T. Moura ◽  
José C. Ferreira-Silva ◽  
Pamela Ramos-Deus ◽  
Priscila G. C. Silva ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Embryonic Development ◽  
Blastocyst Stage ◽  
Tunel Assay ◽  
Caspase Activity ◽  
Retinyl Acetate ◽  
Developmental Potential ◽  
Concomitant Reduction ◽  
Lower Capacity

Exposure of caprine oocytes and embryos to retinoids enhances embryonic development, but the mechanisms governing this phenomenon have not been characterised. The aim of the present study was to evaluate if the incidence of apoptosis is affected by the addition of retinyl acetate (RAc) and 9-cis-retinoic acid (RA) during in vitro maturation (IVM) of caprine oocytes. Embryonic development was recorded on days 3 and 8 post-fertilisation, and apoptosis was measured by caspase activity and DNA fragmentation (TUNEL assay). Control zygotes had lower capacity to cleave and reach the blastocyst stage (24.45 ± 2.32 and 5.32 ± 0.81, respectively) than those of RAc- (29.96 ± 1.62 and 7.94 ± 0.93, respectively) and RA-treated groups (30.12 ± 1.51 and 7.36 ± 1.02, respectively). Oocytes and blastocysts positive for TUNEL assay were more frequent, respectively, in the controls (8.20 ± 0.78, 8.70 ± 1.05) than in RAc (5.60 ± 0.52, 4.80 ± 0.51) and RA (6.40 ± 0.69, 5.40 ± 0.69). Caspase activity did not differ between control oocytes (7.20 ± 0.91), RAc (6.60 ± 0.68) and RA (7.30 ± 0.67), but it was reduced in RAc- (5.05 ± 0.62) and RA-treated blastocysts (5.75 ± 0.22) compared to controls (8.35 ± 0.71). These results indicate that the addition of retinoids during IVM increases the developmental potential of goat embryos with a concomitant reduction in apoptosis rates.

scholarly journals Smad Interacting Protein-1 is Essential for Oligodendrocyte Differentiation

2021 ◽  
Author(s):  
Ziwei Chen ◽  
Yuanmei Wang ◽  
Xiaobin Fan ◽  
Jufang Huang ◽  
Chunling Fan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mapk Pathway ◽  
Demyelinating Diseases ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Differentiation ◽  
Interacting Protein ◽  
Erk Mapk ◽  
Cord Injury

Abstract Precursor/stem cell substitutive therapy to promote remyelination is an ideal strategy for central nervous system demyelinating diseases such as spinal cord injury (SCI). However, the microenvironment of the injured area is not conducive to the survival, differentiation, and functions of the transplanted cells. Identifying and regulating the key inhibitory factors might be an important target for the treatment of demyelinating diseases. Smad interacting protein-1 (Sip1) is a transcription factor that binds to phosphorylated R-Smad in the nucleus, which promotes remyelination by inducing the differentiation of oligodendrocytes. In this study, we show that the expression of Sip1 is up-regulated and peaks by 1 day and then returns to normal levels 7 days after SCI. Most Sip1 positive cells were oligodendrocytes. In vitro, Sip1 was weakly expressed in the cytoplasm of oligodendrocyte progenitor cells (OPCs), significantly up-regulated in immature oligodendrocytes, and showed significant nuclear transposition. In contrast, Sip1 expression levels in mature oligodendrocytes decreased to levels similar to those in OPCs. The RNA interference of Sip1 in OPCs reduced the level of myelin basic protein (a mature oligodendrocyte marker protein, MBP) and pERK1/2 (a key molecule of the ERK/MAPK pathway) in oligodendrocytes. These findings suggest that Sip1 is essential for oligodendrocyte differentiation and might affect the ERK/MAPK signal pathway. The results provide a theoretical basis for the treatment of demyelinating lesions such as spinal cord injury by regulating Sip1 expression in oligodendrocytes.

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