Advertisement
JOURNAL ARTICLES
Oligodendrocyte progenitors are generated throughout the embryonic mouse brain, but differentiate in restricted foci
R.J. Hardy, V.L. Friedrich
Development 1996 122: 2059-2069;

Summary

Recent evidence from studies mapping the expression of putative oligodendrocyte progenitor specific mRNAs has suggested that oligodendrocyte progenitors arise during embryogenesis, in specific foci of the neuroectoderm. In order to test this hypothesis, we have assayed different regions of the embryonic central nervous system for their ability to generate oligodendrocytes following transplantation into neonatal cerebrum. To allow identification of donor-derived oligodendrocytes in wild-type host brain, we used the MbetaP transgenic mouse, which expresses lacZ in oligodendrocytes, as donor tissue. We found that tissue fragments derived from several levels of the anterior-posterior axis of the neural tube at E14.5 and E12.5, chosen to include (hindbrain, cervical and lumbar spinal cord), or exclude (dorsal telencephalon) putative foci of oligodendrocyte progenitors, all produced oligodendrocytes following transplantation. In addition, these same regions taken from E10.5, prior to the appearance of putative oligodendrocyte progenitor markers, also all yielded oligodendrocytes on transplantation. This indicates that precursor cells that can generate oligodendrocytes are widespread throughout the neuroectoderm as early as E10.5. We have also used the oligodendrocyte lineage-specific glycolipid antibodies O4, R-mAb and O1 to identify those regions of the developing brain that first support the differentiation of oligodendrocytes from their progenitor cells. We found that the first oligodendrocytes arise in prenatal brain at E14.5, in a restricted zone adjacent to the midline of the medulla. These cells are mitotically inactive, differentiated oligodendrocytes and, using light and electron microscopy, we show that they become functional, myelin-bearing oligodendrocytes. We have mapped the subsequent appearance of differentiated oligodendrocytes in the prenatal brain and show that they appear in a restricted, tract-specific manner. Our results suggest that oligodendrocytes are generated from neuroectodermal cells positioned throughout the rostrocaudal axis of the neural tube, rather than at restricted locations of the neuroectoderm. By contrast, the differentiation of such cells into oligodendrocytes does occur in a restricted manner, consistent with local regulation of oligodendrocyte progenitor differentiation.

Reference

    1. Abney E. R.,
    2. Bartlett P. P.,
    3. Raff M. C.
    (1981) Astrocytes, ependymal cells and oligodendrocytes develop on schedule in dissociated cell cultures of embryonic rat brain. Dev. Biol 83, 301–310
    OpenUrlCrossRefPubMedWeb of Science
    1. Bansal R.,
    2. Steffanson K.,
    3. Pfeiffer S. E.
    (1992) POA, a developmental antigen expressed by A007/O4-positive oligodendrocyte progenitors prior to the appearance of sulfatide and galactocerebroside. J. Neurochem 58, 2221–2229
    OpenUrlCrossRefPubMedWeb of Science
    1. Bansal R.,
    2. Warrington A. E.,
    3. Gard A. L.,
    4. Ranscht B.,
    5. Pfeiffer S. E.
    (1989) Multiple and novel specificities of monoclonal antibodies O1, O4 and R-mAb used in the analysis of oligodendrocyte development. J. Neurosci. Res 24, 548–557
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Puelles L.,
    3. Porteus M. H.,
    4. Frohman M. A.,
    5. Martin G. R.,
    6. Rubenstein J. L. R.
    (1993). Spatially restricted expression of Dlx-1, Dlx-2(Tes-a), Gbx-2 and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and lonitudinal boudaries. J Neurosci 13, 3155–3172
    OpenUrlAbstract
    1. Cameron-Curry P.,
    2. LeDourarin N. M.
    (1995) Oligodendrocyteprecursors originate from both the dorsal and the ventral parts of the spinal cord. Neuron 15, 1299–1310
    OpenUrlCrossRefPubMedWeb of Science
    1. Campagnoni C. W.,
    2. Garbay B.,
    3. Micevych P.,
    4. Pribyl T.,
    5. Kampf K.,
    6. Handley V. W.,
    7. Campagnoni A. T.
    (1992) DM20 mRNA splice product of the myelin protoelipid protein gene is expressed in the murine heart. J. Neurosci. Res 33, 148–155
    OpenUrlCrossRefPubMedWeb of Science
    1. Cheng B.,
    2. Mattson M. P.
    (1995) PDGFs protect hippocampal neurons against energy deprivation and oxidative injury: evidence for induction of antioxidant pathways. J. Neurosci 15, 7095–7104
    OpenUrlAbstract
    1. Davis A.,
    2. Temple S.
    (1994) A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372, 263–266
    OpenUrlCrossRefPubMed
    1. Franklin R. J. M.,
    2. Blakemore W.
    (1995) Glial-cell transplantation and plasticity in the O-2A lineage-implications for CNS repair. Trends Neurosci 18, 151–156
    OpenUrlCrossRefPubMedWeb of Science
    1. Friedrich V. L.,
    2. Lazzarini R. A.
    (1993) Restricted migration of transplanted oligodendrocytes or the progenitors, revealed by transgenic marker MP. J. Neural Transpl. Plasticity 4, 139–146
    OpenUrlPubMedWeb of Science
    1. Friedrich V. L. J.,
    2. Holstein G. R.,
    3. Li X.,
    4. Gow A. A. K. K. A. L. R.
    (1993) Intracellular distribution of transgenic bacterial-galactosidase in central nervous system neurons and neuroglia. J. Neurosci. Res 36, 88–98
    OpenUrlCrossRefPubMedWeb of Science
    1. Gard A. L.,
    2. Pfeiffer S. E.
    (1989) Oligodendrocyte progenitors isolated directly from developing telencephalon at a specific phenotypic stage: myelinogenic potential in a defined environment. Development 106, 119–132
    OpenUrlAbstract
    1. Gonye G. E.,
    2. Warrington A. E.,
    3. DeVito J. A.,
    4. Pfeiffer S. E.
    (1994) Oligodendrocyte precursor quantitation and localization in perinatal brain using a retrospective bioassay. J. Neurosci 14, 5365–5372
    OpenUrlAbstract
    1. Gow A.,
    2. Friedrich V. L., Jr.,
    3. Lazzarini R. A.
    (1992) Myelin basic protein gene contains separate enhancers for oligodendrocyte and Schwann cell expression. J. Cell Biol 119, 605–616
    OpenUrlAbstract/FREE Full Text
    1. Hardy R.,
    2. Reynolds R.
    (1991) Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo. Development 111, 1061–1080
    OpenUrlAbstract/FREE Full Text
    1. Hardy R.,
    2. Reynolds R.
    (1993) Neuron-oligodendroglial interactions during central nervous system development. J. Neurosci. Res 36, 121–126
    OpenUrlCrossRefPubMedWeb of Science
    1. Hardy R.,
    2. Reynolds R.
    (1993) Rat cerebral cortical neurons in primary culture release a mitogen specific for early (Gd3+/O4-) oligodendrocyte progenitors. J. Neurosci. Res 34, 589–600
    OpenUrlCrossRefPubMedWeb of Science
    1. Kioussi C.,
    2. Gross M. K.,
    3. Gruss P.
    (1995) Pax3: A paired domain gene as a regulator in PNS myelination. Neuron 15, 553–562
    OpenUrlCrossRefPubMedWeb of Science
    1. Levine S. M.,
    2. Goldman J. E.
    (1988) Spatial and temporal patterns of oligodendrocyte differentiation in rat cerebrum and cerebellum. J. Comp. Neurol 277, 441–455
    OpenUrlCrossRefPubMedWeb of Science
    1. Levison S. M.,
    2. Goldman J. E.
    (1993) Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10, 201–212
    OpenUrlCrossRefPubMedWeb of Science
    1. Pringle N.,
    2. Richardson W. D.
    (1993) A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. Development 117, 525–533
    OpenUrlAbstract
    1. Pringle N. P.,
    2. Mudhar H. S.,
    3. Collarini E. J.,
    4. Richardson W. D.
    (1992) PDGF receptors in the rat CNS:during late neurogenesis, PDGF-alpha receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. Development 115, 535–551
    OpenUrlAbstract
    1. Ranchst B.,
    2. Clapshaw P. A.,
    3. Price J.,
    4. Noble M.,
    5. Siefert W.
    (1978) Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc. Nat. Acad. Sci. USA 79, 2709–2713
    1. Reynolds B. A.,
    2. Weiss S.
    (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710
    OpenUrlAbstract/FREE Full Text
    1. Reynolds R.,
    2. Wilkin G. P.
    (1988) Development of macroglial cells in rat cerebellum II: An in situ immunohistochemical study of oligodendrocyte lineage from precursor to mature myelinating cell. Development 102, 409–425
    OpenUrlAbstract
    1. Reynolds R.,
    2. Wilkin G. P.
    (1991) Oligodendroglial progenitor cells but not oligodendroglia divide during normal development of the rat cerebellum. J. Neurocytol 20, 216–224
    OpenUrlCrossRefPubMedWeb of Science
    1. Roussel G.,
    2. Nussbaum J. L.
    (1981) Comparative localization of Wolfgram W1 and myelin basic proteins in the rat brain during ontogenesis. Histochem. J 13, 1029–1047
    OpenUrlCrossRefPubMed
    1. Sommer I.,
    2. Schachner M.
    (1981) Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: and immunocytochemical study in the central nervous system. Dev. Biol 83, 311–327
    OpenUrlCrossRefPubMedWeb of Science
    1. Timsit S.,
    2. Martinez S.,
    3. Allinquant B.,
    4. Peyron F.,
    5. Puelles L.,
    6. Zalc B.
    (1995) Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. J. Neurosci 15, 1012–1024
    OpenUrlAbstract
    1. Trousse F.,
    2. Giess M.,
    3. Soula s.,
    4. Ghandou r. S.,
    5. Duprat A.-M.,
    6. Cochard P.
    (1995) Notochord and Floor plate stimulate oligodendrocytedifferentiation in cultures of the chick dorsal neural tube. J. Neurosci. Res 41, 552–560
    OpenUrlCrossRefPubMedWeb of Science
    1. Vignais L.,
    2. Nait-Oumesmar B.,
    3. Baron-Van Evercooren A.
    (1995) PDGF alpha receptor is expressed on mature neurones of the central nervous system. Neuroreport 6, 15–19
    1. Warf B. C.,
    2. Fok-Seang J.,
    3. Miller R. H.
    (1991) Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord. J. Neurosci 11, 2477–2488
    OpenUrlAbstract
    1. Warrington A. E.,
    2. Barbarese E.,
    3. Pfeiffer S. E.
    (1993) Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts. J. Neurosci. Res 34, 1–13
    OpenUrlCrossRefPubMedWeb of Science
    1. Warrington A. E.,
    2. Pfeiffer S. E.
    (1992) Proliferation and differentiation of O4+oligodendrocytes in postnatal rat cerebellum: analysis in unfixed tissue slices using anti-glycolipid antibodies. J. Neurosci. Res 33, 338–353
    OpenUrlCrossRefPubMedWeb of Science
    1. Williams B.,
    2. Price J.
    (1995) Evidence for multiple precursor cell types in the embryonic rat cerebral cortex. Neuron 14, 1181–1188
    OpenUrlCrossRefPubMedWeb of Science
    1. Yu W.-P.,
    2. Collarini E. J.,
    3. Pringle N. P.,
    4. Richardson W. D.
    (1994) Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube. Neuron 12, 1353–1362
    OpenUrlCrossRefPubMedWeb of Science
    1. Zerlin M.,
    2. Levison S. W.,
    3. Goldman J. E.
    (1995) Early patterns of migration, morphogenesis and intermediate filament expression of subventricular zone cells in the postnatal rat forebrain. J. Neurosci 15, 7238–7249
    OpenUrlAbstract
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Oligodendrocyte progenitors are generated throughout the embryonic mouse brain, but differentiate in restricted foci
R.J. Hardy, V.L. Friedrich
Development 1996 122: 2059-2069;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Brandon Carpenter talks about how inherited histone methylation defines the germline versus soma decision in C. elegans. 

Sign up to join our next session:

10 March
Time: TBC
Chaired by: Thomas Lecuit