HPC-7: A novel oligodendrocyte lineage protein which appears prior to galactocerebroside

Baas, Dominique; Barnstable, Colin J.

doi:10.1002/(sici)1098-1136(199806)23:2<169::aid-glia8>3.0.co;2-1

Cited by 8 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1Ac). Immature OLs also express an unknown antigen HPC7 (Baas and Barnstable, 1998) that co-labels with O1 (data not shown) and can be used interchangeably to mark this stage. Immature OLs soon form a thick ring-like structure and begin to express the myelin protein CNP.…”

Section: Resultsmentioning

confidence: 99%

“…Primary antibodies used were anti-Olig2 (1:50, IBL), A2B5 (1:25), O4 (1:25, Bansal et al, 1992), O1 (1:25), anti-HPC7 (1:25, Baas and Barnstable, 1998), anti-CNP and anti-MBP (1:100; Sternberger Monoclonals Incorp., Lutherville, MD),. Secondary antibodies include, FITC-conjugated goat anti-mouse IgM, μ-chain specific, for O4, A2B5 and O1; Cy3-conjugated anti-mouse IgG, gama-chain specific for HCP7, CNP, MBP (Jackson Labs, Bar Harbor, Maine) or anti-rabbit IgG for Olig2, and a nuclear label, Hoechst dye (Sigma).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation

Guardiola-Diaz

Ishii

Bansal

2011

Glia

152

130

View full text Add to dashboard Cite

Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages in a well-coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate the role of extracellular signal-regulated-kinase-1,-2 (Erk1/2) and the mammalian target of rapamycin (mTOR), downstream effectors of the Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways, at specific stages of OL development in vitro. Using a panel of developmental stage-specific antigenic markers and pharmacological inhibitors, we provide evidence that Erk1/2 signaling regulates transition of early progenitors to the late progenitor stage and, as a consequence, to the immature OL stage, but not the transition of immature OL to the mature OL stage. In contrast, mTOR signaling is not required for early progenitor transition to late progenitor stage. Surprisingly, it is also not required for the transition of late progenitors to terminally differentiated immature OLs, as has been reported previously, but is required for the next sequential transition of immature OLs to the mature OL stage. Furthermore, mTOR signaling regulates OL cytoskeletal organization and major myelin protein expression. These in vitro findings correlate with our in vivo data showing that inhibition of mTOR by rapamycin injection attenuated the onset of myelination in the early postnatal brain. Thus, these studies demonstrate that Erk1/2 and mTOR signaling sequentially regulates distinct stages of OL progenitor differentiation and suggest that cells in the OL-lineage require distinct signaling mechanisms to transition through specific stages of their development.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation

Guardiola-Diaz

Ishii

Bansal

2011

Glia

152

130

View full text Add to dashboard Cite

show abstract

“…Since the mutant mice die before OLPs differentiate into OLs, precluding the in vivo analysis of Fgfr function in the maturation of OLs, we also utilized these mutant forebrain cultures to analyze OLP terminal differentiation by examining OL marker, HPC7, whose expression overlaps with galactocerebroside, a well-recognized marker of OLs (Pfeiffer et al ., 1993; Baas and Barnstable, 1998). HPC7 immunolabeling was detected in the cultures of Fgfr1−/− and Fgfr2−/− mutants similar to controls, demonstrating that the small numbers of OLPs that were produced in these mutant cultures were able to differentiate into OLs.…”

Section: Resultsmentioning

confidence: 99%

“…Pre/early OLPs were identified with Olig2 and PDGFRa antibodies, late OLPs with O4 antibody, and mature OLs with HPC7 antibody (Pfeiffer et al, 1993; Baas and Barnstable, 1998). …”

Section: Methodsmentioning

confidence: 99%

Fibroblast Growth Factor Signaling Is Required for the Generation of Oligodendrocyte Progenitors from the Embryonic Forebrain

Furusho¹,

Kaga²,

Ishii³

et al. 2011

J. Neurosci.

103

View full text Add to dashboard Cite

Fibroblast growth factors (FGFs) comprise a family of developmental regulators implicated in a wide variety of neurological functions. FGF receptors-1,-2,-3 (Fgfrs) are expressed in the embryonic forebrain, including regions overlapping with ventral sites of oligodendrocyte progenitor (OLP) generation. Although FGF signaling is known to influence the proliferation of OLPs in vitro, functions of different Fgfrs in vivo are lacking. Here, we examined single and double mutants with conditional disruption of Fgfrs, specifically in the embryonic forebrain, to investigate the effect of FGFs on the generation and proliferation of OLPs in vivo. FGF signaling, through cooperation between Fgfr1 and Fgfr2 but not Fgfr3, is required for the initial generation of OLPs in the mouse ventral forebrain, with Fgfr1 being a stronger inducer than Fgfr2. In cultures derived from embryonic mutant forebrains or from normal forebrains grown in the presence of Fgfr inhibitor, a strong attenuation of OLP generation was observed, supporting the role of FGF signaling in vivo. Contrary to in vitro findings, Fgfr1 and Fgfr2 signaling is not required for the proliferation of OLPs in vivo. Finally, failure of OLP generation in the Fgfr mutants occurred without loss of sonic hedgehog (Shh) signaling; and pharmacological inhibition of either Fgfr or hedgehog signaling in parallel cultures strongly inhibited OLP generation, suggesting that Fgfrs cooperate with Shh to generate OLPs. Overall, our results reveal for the first time an essential role of FGF signaling in vivo, where the three Fgfrs differentially control the normal generation of OLPs from the embryonic ventral forebrain.

show abstract

“…RGC axons were detected by using an antibody directed against the phosphorylated 70-kDa neurofilament protein (Dako). Terminally differentiated oligodendrocytes were stained with an antibody directed against the myelin basic protein (25 mice. At this time, OPC were identified on optic nerve sections in all mice by using the NG2 antibody, confirming recent results obtained for TR␤ Ϫ/Ϫ mice (16).…”

Section: Methodsmentioning

confidence: 99%

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Baas

Legrand

Samarut

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Thyroid hormone (3,5,3-triiodo-L-thyronine or T3) exerts a pleiotropic activity during central nervous system development. Hypothyroidism during the fetal and postnatal life results in an irreversible mental retardation syndrome. At the cellular level, T3 is known to act on neuronal and glial lineages and to control cell proliferation, apoptosis, migration, and differentiation. Oligodendrocyte precursor cells (OPC) found at birth in the optic nerves are self-renewing cells that normally differentiate during the first 3 weeks of rodent postnatal life into postmitotic myelinating oligodendrocytes. In vitro, the addition of T3 to OPC is sufficient to trigger their terminal differentiation. The present analysis of T3 receptor knockout mice reveals that the absence of all T3 receptor results in the persistence of OPC proliferation in adult optic nerves, in a default in myelination, and sometimes in the degeneration of the retinal ganglion neurons. Thus, T3 signaling is necessary in vivo to promote the complete differentiation of OPC. T hyroid hormone (3,5,3Ј-triiodo-L-thyronine, T3) acts directly at the transcription level by binding to nuclear receptors (TR␣1 and TR␤1, TR␤2, TR␤3) encoded by both TR␣ and TR␤ genes to control a number of physiological and developmental processes. During the late embryonic postnatal period, T3 action is critical for brain development. However, although both hyperthyroidism and hypothyroidism are known to affect directly or indirectly the proliferation, apoptosis, migration, and differentiation of several neuronal and glial cell types (1, 2), only subtle brain defects have been reported to date in the nervous system of TR knockout mice (3, 4). Moreover, knock-in point mutations recently led to contrasting results that are difficult to interpret (5-7). In the rodent optic nerves, oligodendrocyte precursor cells (OPC) differentiate during the first postnatal weeks to give rise to the oligodendrocytes that synthesize myelin around the axons of the retinal ganglion cells (RGC). The in vitro culture of newborn optic nerve OPC (8-10) has offered a unique opportunity to study the precise influence of T3 on the differentiation of this category of glial cells (reviewed in ref. 10). This in vitro model has been extensively investigated, and a number of studies confirmed the direct effect of T3 on OPC differentiation. However, the fact that retinoic acid or glucocorticoids can substitute to T3 to trigger in vitro OPC differentiation (9, 11) raises the question of the respective importance of these factors in vivo. The respective contribution of TR␣ and TR␤ in OPC hormonal response is also unclear (8,10,12). TR␣ is expressed at all stages of oligodendrocyte differentiation, whereas the status for TR␤ remains controversial. Based on RNA and protein analysis, TR␤ expression has been reported to be restricted to differentiated oligodendrocytes (13-16) or to occur in both OPC and oligodendrocytes (9, 17). To clarify the importance of T3 action in vivo and the respective functions of TR␣ and TR␤ in OPC...

show abstract

HPC-7: A novel oligodendrocyte lineage protein which appears prior to galactocerebroside

Cited by 8 publications

References 38 publications

Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation

Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation

Fibroblast Growth Factor Signaling Is Required for the Generation of Oligodendrocyte Progenitors from the Embryonic Forebrain

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Contact Info

Product

Resources

About