Insulin-like growth factor I (IGF-I) strongly stimulates the generation of differentiated neurons in cultures of neuroepithelial cells of the embryonic chick neural retina in the presence of a laminin-1 tissue culture substrate. Treatment of cultured neuroepithelial cells with IGF-I rapidly up-regulated the mRNA coding for the alpha 6 integrin subunit whereas specific reduction of alpha 6 subunit levels by treatment with an alpha 6 integrin antisense oligonucleotide resulted in reduced neuronal differentiation in vitro. Although IGF-I immunoreactivity is seen throughout the neural retina, expression of IGF-I mRNA is confined to the pigment epithelium during the period of neurogenesis in vivo. Neutralization of the endogenous IGF-I with a blocking antibody down-regulated levels of alpha 6 integrin mRNA and reduced the production of differentiated retinal neurons in vivo. These data indicate a role for IGF-I in the generation of retinal neurons mediated by the interaction of laminin with its alpha 6 integrin subunit-containing receptor.

Reference

Beck
K. D.
,
Powell-Braxton
L.
,
Widmer
H.-R.
,
Valverde
J.
,
Hefti
F.
(
1995
)
IGF1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hyppocampal granule and striatal parvalbumin-containing neurons.
Neuron
14
,
717
730
Bondy
C. A.
(
1991
)
Transient IGF-I gene expression during the maturation of functionally related central projection neurons.
J. Neurosci
11
,
3442
3455
Bossy
B.
,
Reichardt
L. F.
(
1990
)
Chick integrinv subunit molecular analysis reveals high conservation of structural domains and association with multiple subunits in embryo fibroblasts.
Biochemistry
29
,
10191
10198
Bottenstein
J.
,
Sato
G. H.
(
1979
)
Growth of a rat neuroblastoma cell line in a serum-free supplemented medium.
Proc. Nat. Acad. Sci. USA
76
,
514
517
Bronner-Fraser
M.
,
Artinger
M.
,
Muschler
J.
,
Horvitz
A. F.
(
1992
)
Developmentally regulated expression of6integrin in avian embryos.
Development
115
,
1321
1330
Chomczynski
P.
,
Sacchi
N.
(
1987
)
Single step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction.
Analyt. Biochem
162
,
156
159
Church
G. M.
,
Gilbert
W.
(
1984
)
Genomic sequencing.
Proc. Nat. Acad. Sci. USA
81
,
1991
1995
Cohen
J.
,
Burne
J. F.
,
McKinlay
C.
,
Winter
J.
(
1987
)
The role of laminin and the laminin/fibronectin receptor complex in the outgrowth of retinal ganglion cell axons.
Dev. Biol
122
,
407
418
Cohick
W. S.
,
Clemmons
D. R.
(
1993
)
The insulin-like growth factors.
Annu. Rev. Physiol
55
,
131
153
Collins
F.
(
1978
)
Axon initiation by ciliary neurons in culture.
Dev. Biol
65
,
50
57
De Curtis
I.
,
Quaranta
V.
,
Tamura
R. N.
,
Reichardt
L. F.
(
1991
)
Laminin receptors in the retina: sequence analysis of the chick integrin6subunit. Evidence for transcriptional and posttranscriptional regulation.
J. Cell Biol
113
,
405
416
De Curtis
I.
,
Reichardt
L. F.
(
1993
)
Function and spatial distribution in the developing chick retina of the laminin receptor6 1and its isoforms.
Development
118
,
377
388
De la Rosa
E. J.
,
Bondy
C. A.
,
Hernandez-Sanchez
C.
,
Wu
X.
,
Zhou
J.
,
L¢pez-Carranza
A.
,
Scavo
L. M.
,
de Pablo
F.
(
1994
)
Insulin and insulin-like growth factor system components gene expression in the chick from early neurogenesis until late development and the effect on neuroepithelial cells.
Eur. J. Neurosci
6
,
1801
1810
Florini
J. R.
,
Ewton
D. Z.
,
Roof
S. L.
(
1991
)
IGF-I stimulates terminal myogenic differentiation by induction of myogenin gene expression.
Mol. Endocrinol
5
,
718
724
Frade
J. M.
,
Martínez-Morales
J. R.
,
Rodríguez-Tebar
A.
(
1996
)
Laminin-1 selectively stimulates neuron generation from cultured retinal neuroepithelial cells.
Exp. Cell Res
222
,
140
149
Hall
D. E.
,
Reichardt
L. F.
,
Crowley
E.
,
Holley
B.
,
Moezzi
H.
,
Sonnenberg
A.
,
Damsky
C. H.
(
1990
)
The1/ 1and6/ 1integrin heterodimers mediate cell attachment to distinct sites on laminin.
J. Cell Biol
110
,
2175
2184
Hamburger
V.
,
Hamilton
H.
(
1951
)
A series of normal stages in the development of chick embryo.
J. Morphol
88
,
49
92
Huang
P.
,
Plunkett
W.
(
1992
)
A quantitative assay for fragmented DNA in apoptotic cells.
Analyt. Biochem
207
,
163
167
Kost
T. A.
,
Theodorakis
N.
,
Hughes
S. H.
(
1983
)
Nucleotide sequence of the chick cytoplasmic-actin gene.
Nucl. Acids Res
11
,
8287
8301
Lee
W.-H.
,
Javedan
S.
,
Bondy
C. A.
(
1992
)
Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development.
J. Neurosci
12
,
4737
4744
Prada
C.
,
Puga
J.
,
Lopez-Mendez
L.
,
Lopez
R.
,
Ramírez
G.
(
1991
)
Spatial and temporal patterns of neurogenesis in the chick retina.
Eur. J. Neurosci
3
,
559
569
Rager
G.
(
1980
)
Development of the retino-tectal projection in the chick retina.
Adv. Anat. Embryol. Cell Biol
63
,
1
92
Rathjen
F. G.
,
Wolf
J. M.
,
Franck
R.
,
Bonhoeffer
F.
,
Rutishauser
U.
(
1987
)
Membrane glycoproteins involved in neurite fasciculation.
J. Cell Biol
104
,
343
353
Rodríguez-Tebar
A.
,
Jeffrey
P. L.
,
Thoenen
H.
,
Barde
Y.-A.
(
1989
)
The survival of chick retinal ganglion cells in response to brain-derived neurotrophic factor depends on their embryonic age.
Dev. Biol
136
,
296
303
Rohrer
H.
(
1990
)
The role of growth factors in the control of neurogenesis.
Eur. J. Neurosci
2
,
1005
1015
Rohrer
H.
,
Hofer
M.
,
Hellweg
R.
,
Korshing
S.
,
Stehle
A. D.
,
Saadat
S.
,
Thoenen
H.
(
1988
)
Antibodies against nerve growth factor interfere in vivo with the development of avian sensory and sympathetic neurons.
Development
103
,
545
552
Ruan
W.
,
Newman
C. B.
,
Kleinberg
D. L.
(
1992
)
Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammarygland differentiation and development.
Proc. Nat. Acad. Sci. USA
89
,
10872
10876
Russell
W. E.
,
Van Wyk
J. J.
,
Pledger
W. J.
(
1984
)
Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C.
Proc. Nat. Acad. Sci. USA
81
,
2389
2392
Sonnenberg
A.
,
Modderman
P. W.
,
Hogervorst
F.
(
1988
)
Laminin receptor on platelets is the integrin VLA-6.
Nature
336
,
487
489
Steele
F. R.
,
Chader
G. J.
,
Johnson
L. V.
,
Tombran-Tink
J.
(
1992
)
Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family.
Proc. Nat. Acad. Sci. USA
90
,
1526
1530
Steele-Perkins
G.
,
Turner
J.
,
Edman
J. C.
,
Hari
J.
,
Pierce
S. B.
,
Stover
C.
,
Rutter
W. J.
,
Roth
R. A.
(
1988
)
Expression and characterization of a functional human insulin-like growth factor I receptor.
J. Biol. Chem
263
,
11486
11492
Turner
D. L.
,
Cepko
C. L.
(
1987
)
A common progenitor for neurons and glia persists in rat retina late in development.
Nature
328
,
131
136
Vennström
B.
,
Bishop
M. J.
(
1982
)
Isolation and Characterization of chick DNA homologous to the two putative oncogenes of avian erythroblastosis virus.
Cell
28
,
135
143
Waldbillig
R. J.
,
Arnold
D.
,
Fletcher
R. T.
,
Chader
G. J.
(
1991
)
Insulin and IGF-I binding in developing chick neural retina and pigment epithelium: a characterization of binding and structural differences.
Exp. Eye Res
53
,
13
22
Wilkinson
D. G.
,
Nieto
M. A.
(
1993
)
Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts.
Meth. Enzymol
225
,
361
373
Zackenfels
K.
,
Oppenheim
R. W.
,
Rohrer
H.
(
1995
)
Evidence for an important role of IGF-I and IGF-II for the early development of chick sympathetic neurons.
Neuron
14
,
731
741
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