We have examined the expression of integrins on primary oligodendroglial cells during the differentiation of the proliferative oligodendrocyte precursor (O-2A progenitor) cell to the postmitotic oligodendrocyte. Cells of the oligodendrocyte lineage expressed a limited repertoire of integrins: alpha 6 beta 1 and alpha v integrins including alpha v beta 1, alpha v beta 3 and alpha v beta 5, as well as a potentially novel integrin alpha v beta 80 kDa. Integrin expression was developmentally regulated; during differentiation alpha v beta 1 was reduced and alpha v beta 5 upregulated. These results suggest that laminin and vitronectin are important extracellular matrix ligands for oligodendrocytes, and provide a rational explanation for previous observations that RGD peptides inhibit the expression of myelin-specific genes. They also suggest a simple model by which switching of integrin beta subunits might regulate differentiation. As chimeric beta 1 integrins with a beta 5 cytoplasmic domain support proliferation less well than normal beta 1 integrins (Pasqualini and Hemler (1994), J. Cell Biol. 125, 447–460) the switch from alpha v beta 1 to alpha v beta 5 might play a key instructive role in the cessation of proliferation and subsequent differentiation.

REFERENCES

Adams
J. C.
,
Watt
F. M.
(
1993
)
Regulation of development and differentiation by the extracellular matrix.
Development
117
,
1183
98
Armstrong
R. C.
,
Harvath
L.
,
Dubois-Dalcq
M. E.
(
1990
)
Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules.
J. Neuroscience Res
27
,
400
407
Bartsch
S.
,
Bartsch
U.
,
Dorries
U.
,
Faissner
A.
,
Weller
A.
,
Ekblom
P.
,
Schachner
M.
(
1992
)
Expression of tenascin in the developing and adult cerebellar cortex.
J. Neurosci
12
,
736
749
Barres
B. A.
,
Hart
I. K.
,
Coles
H. S. R.
,
Burne
J. F.
,
Voyvodic
J. T.
,
Richardson
W. D.
,
Raff
M. C.
(
1992
)
Cell death and control of cell survival in the oligodendrocyte lineage.
Cell
70
,
31
46
Barres
B. A.
,
Raff
M. C.
(
1994
)
Control of oligodendrocyte number in the developing rat optic nerve.
Neuron
12
,
935
942
Bodary
S. C.
,
McLean
J. W.
(
1990
)
The integrin1 subunit associates with the vitronectin receptor v subunit to form a novel vitronectin receptor in a human embryonic kidney cell line.
J. Biol. Chem
265
,
5938
5941
Bossy
B.
,
Bossy-Wetzel
E.
,
Reichardt
L. F.
(
1991
)
Characterization of the integrin8 subunit: a new integrin 1-associated subunit, which is prominently expressed on axons and on cells in contact with basal laminae in chick embryos.
EMBO J
10
,
2375
2385
Busk
M.
,
Pytela
R.
,
Sheppard
D.
(
1992
)
Characterization of the integrinv 6 as a fibronectin-binding protein.
J. Biol. Chem
267
,
5790
5796
Cardwell
M. C.
,
Rome
L. H.
(
1988
)
Evidence that an RGD-dependent receptor mediates the binding of oligodendrocytes to a novel ligand in a glial-derived matrix.
J. Cell Biol
107
,
1541
1549
Cardwell
M. C.
,
Rome
L. H.
(
1988
)
RGD-containing peptides inhibit the synthesis of myelin-like membrane by cultured oligodendrocytes.
J. Cell Biol
107
,
1551
1559
Cheresh
D. A.
,
Smith
J. W.
,
Cooper
H. M.
,
Quaranta
V.
(
1989
)
A novel vitronectin receptor integrin (v x) is responsible for distinct adhesive properties of carcinoma cells.
Cell
57
,
59
69
Cheresh
D. A.
,
Spiro
R. C.
(
1987
)
Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell adhesion to vitronectin, fibrinogen and Von Willebrand factor.
J. Biol. Chem
262
,
17703
17711
Cohen
J.
,
Burne
J. F.
,
Winter
J.
,
Bartlett
P. F.
(
1986
)
Retinal ganglion cells lose response to laminin with maturation.
Nature
322
,
465
467
Cooper
H. M.
,
Tamura
R. N.
,
Quaranta
V.
(
1991
)
The major laminin receptor of mouse embryonic stem cells is a novel isoform of the6 1 integrin.
J. Cell Biol
115
,
843
850
de Curtis
I.
,
Quaranta
V.
,
Tamura
R. N.
,
Reichardt
L. F.
(
1991
)
Laminin receptors in the retina: sequence analysis of the chick integrin6 subunit. Evidence for transcriptional and posttranslational regulation.
J. Cell Biol
113
,
405
416
Diamond
M. S.
,
Springer
T. A.
(
1994
)
The dynamic regulation of integrin adhesiveness.
Curr. Biol
4
,
506
517
Dubois-Dalcq
M.
,
Behar
T.
,
Hudson
L.
,
Lazzarini
R. A.
(
1986
)
Emergence of three myelin proteins in oligodendrocytes cultured without neurones.
J. Cell Biol
102
,
384
392
Einheber
S.
,
Milner
T. A.
,
Giancotti
F.
,
Salzer
J. L.
(
1993
)
Axonal regulation of Schwann cell integrin expression suggests a role for6 4 in myelination.
J. Cell Biol
123
,
1223
1236
Feltri
M. L.
,
Scherer
S. S.
,
Nemni
R.
,
Kamholz
J.
,
Vogelbacker
H.
,
Scott
M. O.
,
Canal
N.
,
Quaranta
V.
,
Wrabetz
L.
(
1994
)
4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent.
Development
120
,
1287
1301
Galileo
D. S.
,
Majors
J.
,
Horwitz
A. F.
,
Sanes
J. R.
(
1992
)
Retrovirally introduced antisense integrin RNA inhibits neuroblast migration in vivo.
Neuron
9
,
1117
1131
Helfrich
M. H.
,
Nesbitt
S. A.
,
Horton
M. A.
(
1992
)
Integrins on rat osteoclasts: characterization of two monoclonal antibodies (F4 and F11) to rat3.
J. Bone and Min. Res
7
,
345
351
Hemler
M. E.
(
1990
)
VLA proteins in the integrin family: Structures, functions and their role on leucocytes.
Ann. Rev. Immunol
8
,
365
400
Hemler
M. E.
,
Crouse
C.
,
Sonnennberg
A.
(
1989
)
Association of the VLA6 subunit with a novel protein. A possible alternative to the common VLA 1 subunit on certain cell lines.
J. Biol. Chem
264
,
6529
6535
Hemler
M. E.
,
Crouse
C.
,
Takada
Y.
,
Sonnenberg
A.
(
1988
)
Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibronectin receptor) and VLA-6 structures.
J. Biol. Chem
264
,
6529
6535
Hierck
B. P.
,
Thorsteinstottir
S.
,
Niessen
C.
,
Freund
E.
,
Iperen
L. V.
,
Feyen
A.
,
Hogervorst
F.
,
Poelmann
R. E.
,
Mummery
C. L.
,
Sonnenberg
A.
(
1993
)
Variants of the6 1 laminin receptor in early murine development: Distribution, molecular cloning and chromosomal localization of the mouse integrin6 subunit.
Cell Adhesion and Communication
1
,
33
53
Hogervorst
F.
,
Admiraal
L. G.
,
Niessen
C.
,
Kuikman
I.
,
Janssen
H.
,
Daams
H.
,
Sonnenberg
A.
(
1993
)
Biochemical characterization and tissue distribution of the A and B variants of the integrin6 subunit.
J. Cell Biol
121
,
179
191
Hogervorst
F.
,
Kuikman
I.
,
Van Kessel
A. D.
,
Sonnenberg
A.
(
1991
)
Molecular cloning of the human6 integrin subunit. Alternative splicing of 6 mRNA and chromosomal localization of the6 and 4 genes.
Eur. J. Biochem
199
,
425
433
Huxley
A. F.
,
Stampfli
R.
(
1949
)
Evidence for saltatory conduction in peripheral myelinated nerve fibres.
J. Physiol
108
,
315
339
Hynes
R. O.
(
1987
)
Integrins: a family of cell surface receptors.
Cell
48
,
549
554
Hynes
R. O.
(
1992
)
Integrins: Versatility, modulation and signaling in cell adhesion.
Cell
69
,
11
25
Hynes
R. O.
,
Lander
A. D.
(
1992
)
Contact and adhesive specificites in the associations, migrations, and targeting of cells and axons.
Cell
68
,
303
322
Kajiji
S.
,
Tamura
R. N.
,
Quaranta
V.
(
1989
)
A novel integrin (e 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors.
EMBO J
8
,
673
680
Kennel
S. J.
,
Foute
L. J.
,
Falcioni
R.
,
Sonnenberg
A.
,
Stringer
C. D.
,
Crouse
C.
,
Hemler
M. E.
(
1989
)
Analysis of the tumour associated antigen TSP-180. Identity with6 4 in the integrin superfamily.
J. Biol. Chem
264
,
15515
15521
Kiernan
B. W.
,
ffrench-Constant
C.
(
1993
)
Oligodendrocyte precursor (O-2A progenitor) cell migration; a model system for the study of cell migration in the developing central nervous system.
Development
1993
,
219
225
Koivunen
E.
,
Gay
D. A.
,
Ruoslahti
E.
(
1993
)
Selection of peptides binding to the5 1 integrin from phage display library.
J. Biol. Chem
268
,
20205
20210
Lawler
J.
,
Hynes
R. O.
(
1989
)
An integrin receptor on normal and thrombasthenic platelets that binds thrombospondin.
Blood
74
,
2022
2027
Leavesley
D. I.
,
Ferguson
G. D.
,
Wayner
E. A.
,
Cheresh
D. A.
(
1992
)
Requirement of the integrin3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen.
J. Cell Biol
117
,
1101
1107
Liesi
P.
(
1985
)
Do neurons in the vertebrate CNS migrate on laminin?.
EMBO J
4
,
1163
1170
Louis
J. C.
,
Magal
E.
,
Muir
D.
,
Manthorpe
M.
,
Varon
S.
(
1992
)
CG-4, a new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type-2 astrocytes.
J. Neuroscience Res
31
,
193
204
Malek-Hedayat
S.
,
Rome
L. H.
(
1994
)
Expression of a1-related integrin by oligodendroglia in primary culture: evidence for a functional role in myelination.
J. Cell Biol
124
,
1039
1046
Marcantonio
E. E.
,
Hynes
R. O.
(
1988
)
Antibodies to the conserved cytoplasmic domain of the integrin1 subunit react with proteins in vertebrates, invertebrates and fungi.
J. Cell Biol
106
,
1765
1772
Marusich
M. F.
,
Weston
J. A.
(
1991
)
Development of the neural crest.
Curr. Opin. Genet. Dev
1
,
221
229
McCarthy
K. D.
,
De Vellis
J.
(
1980
)
Preparation of separate astroglial and oligodendroglia cell cultures from rat cerebral tissue.
J. Cell Biol
85
,
890
902
McLoon
S. C.
,
McLoon
L. K.
,
Palm
S. L.
,
Furcht
L. T.
(
1988
)
Transient expression of laminin in the optic nerve of the developing rat.
J. Neurosci
8
,
1981
1990
Moyle
M.
,
Napier
M. A.
,
McLean
J. W.
(
1991
)
Cloning and expression of a divergent integrin subunit8.
J. Biol. Chem
266
,
19650
19658
Neugebauer
K. M.
,
Emmett
C. J.
,
Venstrom
K. A.
,
Reichardt
L. F.
(
1991
)
Vitronectin and thrombospondin promote retinal neurite outgrowth: developmental regulation and role of integrins.
Neuron
6
,
345
358
Neugebauer
K. M.
,
Reichardt
L. F.
(
1991
)
Cell surface regulation of1-integrin activity on developing retinal neurons.
Nature
350
,
68
71
Niessen
C. M.
,
Cremona
O.
,
Daams
H.
,
Ferraresi
S.
,
Sonnenberg
A.
,
Marchisio
P. C.
(
1994
)
Expression of the integrin6 4 in peripheral nerves: localization in Schwann and perineural cells and different variants of the4 subunit.
J. Cell Sci
107
,
543
552
Noble
M.
,
Murray
K.
,
Stroobant
P.
,
Waterfield
M. D.
,
Riddle
P.
(
1988
)
Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell.
Nature
333
,
560
562
O'Shea
K. S.
,
Rheinheimer
J. S. T.
,
Dixit
V. M.
(
1990
)
Deposition and role of thrombospondin in the histogenesis of the cerebellar cortex.
J. Cell Biol
110
,
1275
1283
Palmer
E. L.
,
Ruegg
C.
,
Ferrando
R.
,
Pytela
R.
,
Sheppard
D.
(
1993
)
Sequence and tissue distribution of the integrin9 subunit, a novel partner of 1 that is widely distributed in epithelia and muscle.
J. Cell Biol
123
,
1289
1297
Pasqualini
R.
,
Hemler
M. E.
(
1994
)
Contrasting roles for integrin1 and 5 cytoplasmic domains in subcellular localization, cell proliferation and cell migration.
J. Cell Biol
125
,
447
460
Payne
H. R.
,
Lemmon
V.
(
1993
)
Glial cells of the O-2A lineage bind preferentially to N-Cadherin and develop distinct morphologies.
Dev. Biol
159
,
595
607
Plow
E. F.
,
Pierschbacher
M. D.
,
Ruoslahte
E.
,
Marguerie
G. A.
,
Ginsberg
M. H.
(
1985
)
The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets.
Proc. Nat. Acad. Sci. USA
82
,
8057
8061
Prieto
A. L.
,
Edelman
G. M.
,
Crossin
K. L.
(
1993
)
Multiple integrins mediate cell attachment to cytotactin/tenascin.
Proc. Nat. Acad. Sci. USA
90
,
10154
10158
Pringle
N. P.
,
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 oligodendroglial lineage.
Development
117
,
525
533
Pytela
R.
,
Pierschbacher
M. D.
,
Ruoslahti
E.
(
1985
)
A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin.
Proc. Nat. Acad. Sci. USA
82
,
5766
5770
Pytela
R.
,
Pierschbacher
M. D.
,
Ruoslahti
E.
(
1985
)
Identification and isolation of a 140kDa cell surface glycoprotein with properties expected of a fibronectin receptor.
Cell
40
,
191
198
Raff
M. C.
,
Abney
E. R.
,
Fok-Seang
J.
(
1985
)
Reconstitution of a developmental clock in vitro: a critical role for astrocytes in the timing of oligodendrocyte differentiation.
Cell
42
,
61
69
Raff
M. C.
,
Mirsky
R.
,
Fields
R. P.
,
Lisak
S. H.
,
Dorfman
S. H.
,
Silberberg
D. H.
,
Gregson
N. A.
,
Liebowitz
S.
,
Kennedy
M. C.
(
1978
)
Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture.
Nature
274
,
813
816
Ramaswamy
H.
,
Hemler
M. E.
(
1990
)
Cloning, primary structure and properties of a novel human integrinsubunit.
EMBO J
9
,
1561
1568
Ranscht
B.
,
Clapshaw
P. A.
,
Price
J.
,
Noble
M.
,
Seifert
W.
(
1982
)
Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside.
Proc. Natl. Acad. Sci. USA
79
,
2709
2713
Ruoslahti
E.
(
1991
)
Integrins.
J. Clin. Invest
87
,
1
5
Sheppard
A. M.
,
Hamilton
S. K.
,
Pearlman
A. L.
(
1991
)
Changes in the distribution of extracellular matrix components accompany early morphogenetic changes of mammalial cortical development.
J. Neurosci
11
,
3928
3942
Sheppard
D.
,
Rozzo
C.
,
Starr
L.
,
Quaranta
V.
,
Erle
D. J.
,
Pytela
R.
(
1990
)
Complete amino acid sequence of a novel integrinsubunit (6) identified in epithelial cells using the polymerase chain reaction.
J. Biol. Chem
265
,
11502
11507
Small
R. K.
,
Riddle
P.
,
Noble
M.
(
1987
)
Evidence for migration of oligodendrocyte-type-2 astrocyte progenitor cells into the developing rat optic nerve.
Nature
328
,
155
7
Song
W. K.
,
Wang
W.
,
Foster
R. F.
,
Bielser
D. A.
,
Kaufman
S. J.
(
1992
)
H36-alpha 7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis.
J. Cell Biol
117
,
643
657
Sonnenberg
A.
,
Janssen
H.
,
Hogervorst
F.
,
Calafat
J.
,
Hilgers
J.
(
1987
)
A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody.
J. Biol. Chem
262
,
10376
383
Sonnenberg
A.
,
Modderman
P. W.
,
Hogervorst
F.
(
1988
)
Laminin receptor on platelets is the integrin VLA-6.
Nature
336
,
487
489
Sriramarao
P.
,
Mendler
M.
,
Bourdon
M. A.
(
1993
)
Endothelial cell attachment and spreading on human tenascin is mediated by2 1 andv 3 integrins.
J. Cell Sci
105
,
1001
1012
Tamura
R. N.
,
Cooper
H. M.
,
Collo
G.
,
Quaranta
V.
(
1991
)
Cell type-specific integrin variants with alternativechain cytoplasmic domains.
Proc. Nat. Acad. Sci. USA
88
,
10183
10187
Tawil
N.
,
Wilson
P.
,
Carbonetto
S.
(
1993
)
Integrins in point contacts mediate cell spreading: factors that regulate integrin accumulation in point contacts vs. focal contacts.
J. Cell Biol
120
,
261
271
Temple
S.
,
Raff
M. C.
(
1985
)
Differentiation of a bipotential glial progenitor cell in single cell microculture.
Nature
313
,
223
225
Vogel
B. E.
,
Tarone
G.
,
Giancotti
F. G.
,
Gailit
J.
,
Ruoslahti
E.
(
1990
)
A novel fibronectin receptor with an unexpected subunit composition (v 1).
J. Biol. Chem
265
,
5934
5937
Warf
B. C.
,
Fok-Seang
J.
,
Miller
R. H.
(
1991
)
Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord.
J. Neuroscience
11
,
2477
2488
Wayner
E. A.
,
Orlando
R. A.
,
Cheresh
D. A.
(
1991
)
Integrinsv 3 andv 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.
J. Cell Biol
113
,
919
929
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