Abstract
In the adult central nervous system, two distinct populations of glial cells expressing the chondroitin sulfate proteoglycan NG2 have been described: bipolar progenitor cells and more differentiated "synantocytes." These cells have diverse neurological functions, including critical roles in synaptic transmission, repair, and regeneration. Despite their potential importance, the genetic factors that regulate NG2 cell development are poorly understood, and the relationship of synantocytes to the oligodendroglial lineage, in particular, remains controversial. Here, we show that >90% of embryonic and adult NG2 cells express Olig2, a basic helix-loop-helix transcription factor required for oligodendrocyte lineage specification. Analysis of mice lacking Olig function demonstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus. These findings show a general requirement for Olig function in NG2 cell development and highlight further roles for Olig transcription factors in neural progenitor cells.
MeSH Terms
Animals
Antigens/metabolism
Basic Helix-Loop-Helix Transcription Factors/genetics,metabolism
Brain/anatomy & histology,embryology,metabolism
Cell Lineage
Embryo, Mammalian/anatomy & histology,physiology
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins/genetics,metabolism
Neurons/cytology,physiology
Oligodendrocyte Transcription Factor 2
Oligodendroglia/cytology,physiology
Proteoglycans/metabolism
Spinal Cord/cytology,embryology,metabolism
Stem Cells/cytology,physiology
Chemicals
Antigens
Basic Helix-Loop-Helix Transcription Factors
Nerve Tissue Proteins
OLIG2 protein, human
Olig2 protein, mouse
Oligodendrocyte Transcription Factor 2
Proteoglycans
chondroitin sulfate proteoglycan 4
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ligon Keith L
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. keith_ligon@dfci.harvard.edu
Kesari Santosh
Kitada Masaaki
Sun Tao
Arnett Heather A
Alberta John A
Anderson David J
Stiles Charles D
Rowitch David H
References (35)
35 references, click to expand
-
The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages.
Curr Biol. 2002 Jul 9;12(13):1157-63
PMID: 12121626
-
Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum.
Neuron. 2005 Jun 2;46(5):773-85
PMID: 15924863
-
Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection.
Cell. 2002 Apr 5;109(1):75-86
PMID: 11955448
-
Identification of human brain tumour initiating cells.
Nature. 2004 Nov 18;432(7015):396-401
PMID: 15549107
-
The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification.
Cell. 2002 Apr 5;109(1):61-73
PMID: 11955447
-
Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells.
J Neurosci. 2005 Aug 10;25(32):7289-98
PMID: 16093378
-
Neuronal fate determinants of adult olfactory bulb neurogenesis.
Nat Neurosci. 2005 Jul;8(7):865-72
PMID: 15951811
-
Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro.
Clin Immunol. 2002 Jan;102(1):84-95
PMID: 11781071
-
NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors?
J Neurosci Res. 2000 Sep 1;61(5):471-9
PMID: 10956416
-
AN2, the mouse homologue of NG2, is a surface antigen on glial precursor cells implicated in control of cell migration.
J Neurocytol. 2002 Jul-Aug;31(6-7):497-505
PMID: 14501219
-
Mouse NG2+ oligodendrocyte precursors express mRNA for proteolipid protein but not its DM-20 variant: a study of laser microdissection-captured NG2+ cells.
J Neurosci. 2003 Jun 1;23(11):4401-5
PMID: 12805279
-
Synantocytes: the fifth element.
J Anat. 2005 Dec;207(6):695-706
PMID: 16367797
-
Astrocytes and NG2-glia: what's in a name?
J Anat. 2005 Dec;207(6):687-93
PMID: 16367796
-
Cytology and lineage of NG2-positive glia.
J Neurocytol. 2002 Jul-Aug;31(6-7):457-67
PMID: 14501216
-
Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro.
Neuron. 2003 Oct 30;40(3):485-99
PMID: 14642274
-
NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS.
Mol Cell Neurosci. 2003 Oct;24(2):476-88
PMID: 14572468
-
Defining the NG2-expressing cell of the adult CNS.
J Neurocytol. 2002 Jul-Aug;31(6-7):469-80
PMID: 14501217
-
Light and electron microscopic localization of a cell surface antigen (NG2) in the rat cerebellum: association with smooth protoplasmic astrocytes.
J Neurosci. 1987 Sep;7(9):2711-20
PMID: 3305798
-
A fourth type of neuroglial cell in the adult central nervous system.
J Neurocytol. 2004 May;33(3):345-57
PMID: 15475689
-
Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain.
Neuron. 2005 Jan 6;45(1):55-67
PMID: 15629702
-
NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis.
Dev Dyn. 2001 Oct;222(2):218-27
PMID: 11668599
-
Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair.
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18183-8
PMID: 16330768
-
Evidence that perinatal and adult NG2-glia are not conventional oligodendrocyte progenitors and do not depend on axons for their survival.
Mol Cell Neurosci. 2003 Aug;23(4):544-58
PMID: 12932436
-
A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord.
Development. 2005 Apr;132(8):1951-9
PMID: 15790969
-
NG2 cells in the brain: a novel glial cell population.
Hum Cell. 2001 Mar;14(1):77-82
PMID: 11436356
-
The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas.
J Neuropathol Exp Neurol. 2004 May;63(5):499-509
PMID: 15198128
-
Evidence for motoneuron lineage-specific regulation of Olig2 in the vertebrate neural tube.
Dev Biol. 2006 Apr 1;292(1):152-64
PMID: 16469306
-
The oligodendrocyte precursor cell in health and disease.
Trends Neurosci. 2001 Jan;24(1):39-47
PMID: 11163886
-
Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain.
J Neurosci Res. 1996 Feb 01;43(3):299-314
PMID: 8714519
-
Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice.
J Neurosci. 2005 Feb 9;25(6):1354-65
PMID: 15703389
-
Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling.
Neuron. 2005 Jan 6;45(1):41-53
PMID: 15629701
-
NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus.
J Cell Biol. 2004 May 24;165(4):575-89
PMID: 15159421
-
bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.
Science. 2004 Dec 17;306(5704):2111-5
PMID: 15604411
-
Glial specification in the vertebrate neural tube.
Nat Rev Neurosci. 2004 May;5(5):409-19
PMID: 15100723
-
Dorsally derived oligodendrocytes come of age.
Neuron. 2005 Jan 6;45(1):1-3
PMID: 15629694