Patterning of the bipotential retinal primordia (the optic vesicles) into neural retina and retinal pigmented epithelium depends on its interaction with overlaying surface ectoderm. The surface ectoderm expresses FGFs and the optic vesicles express FGF receptors. Previous FGF-expression data and in vitro analyses support the hypothesis that FGF signaling plays a significant role in patterning the optic vesicle. To test this hypothesis in vivo we removed surface ectoderm, a rich source of FGFs. This ablation generated retinas in which neural and pigmented cell phenotypes were co-mingled. Two in vivo protocols were used to replace FGF secretion by surface ectoderm: (1) implantation of FGF-secreting fibroblasts, and (2) injection of replication-incompetent FGF retroviral expression vectors. The retinas in such embryos exhibited segregated neural and pigmented epithelial domains. The neural retina domains were always close to a source of FGF secretion. These results indicate that, in the absense of surface ectoderm, cells of the optic vesicles display both neural and pigmented retinal phenotypes, and that positional cues provided by FGF organize the bipotential optic vesicle into specific neural retina and pigmented epithelium domains. We conclude that FGF can mimic one of the earliest functions of surface ectoderm during eye development, namely the demarcation of neural retina from pigmented epithelium.

REFERENCES

Altshuler
D.
,
LoTurco
J. J.
,
Rush
J.
,
Cepko
C.
(
1993
)
Taurine promotes the differentiation of a vertebrate retinal cell type in vitro.
Development
119
,
1317
1328
Bonicello
E.
,
Gulisano
M.
,
Broccoli
V.
(
1993
)
Emx and Otx homeobox genes in the developing mouse brain.
J. Neurobiol
24
,
1356
1366
Bovolenta
P.
,
Mallamaci
A.
,
Briata
P.
,
Corte
G.
,
Boncinelli
E.
(
1997
)
Implication of OTX2 in pigment epithelium determination and neural retina differentiation.
J. Neuroscience
17
,
4243
4252
Coulombre
J. L.
,
Coulombre
A. J.
(
1965
)
Regeneration of neuronal retina from the pigmented epithelium in the chick embryo.
Dev. Biol
12
,
79
92
DeIongh
R.
,
McAvoy
J. W.
(
1993
)
Spatio-temporal distribution of acidic and basic FGF indicates a role for FGF in rat lens morphogenesis.
Dev. Dyn
198
,
190
202
Detwiler
S. R.
,
VanDyke
R. H.
(
1954
)
Further experimental observations on retinal inductions.
J. Exp. Zool
126
,
135
155
Dorris
F.
(
1938
)
Differentiation of the chick eye in vitro.
J. Exp. Zool
78
,
385
415
Dragomirov
N. I.
(
1937
)
The influence of the neighboring ectoderm on the organization of the eye rudiment.
Dokl. Akad. nauk
15
,
61
64
Furough
R.
,
Zhan
X.
,
MacPhee
M.
,
Friedman
S.
,
Engleka
K. A.
,
Sayers
T.
,
Wiltrout
R. H.
,
Maciag
T.
(
1993
)
Differential transforming abilities of non-secreted and secreted forms of human Fibroblast Growth Factor-1.
J. Biol. Chem
268
,
2960
2968
Grindley
J. C.
,
Davidson
D. R.
,
Hill
R. E.
(
1995
)
The role of Pax-6 in eye and nasal development.
Development
121
,
1433
1442
Guillemot
F.
,
Cepko
C. L.
(
1992
)
Retinal fate and gagnlion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development.
Development
114
,
743
754
Hicks
D.
,
Courtois
Y.
(
1988
)
Acidic fibroblast growth factor stimulates opsin levels in retinal photoreceptor cells in vitro.
FEBS Lett
234
,
475
479
Hicks
D.
,
Courtois
Y.
(
1992
)
Fibroblast growth factor stimulates photorecptor differentiation in vitro.
J. of Neuroscience
12
,
2022
2033
Itoh
N.
,
Mima
T.
,
Mikawa
T.
(
1996
)
Loss of fibroblast growth factor receptors is necessary for terminal differentiation of embryonic limb muscles.
Development
122
,
291
300
Jacobson
A. G.
(
1966
)
Inductive processes in embryonic development.
Science
152
,
25
34
Jeanny
J.-C.
,
Fayein
N.
,
Moenner
M.
,
Chevalier
B.
,
Barritault
D.
,
Courtois
Y.
(
1987
)
Specific fixation of bovine brain and retinal acidic and basic fibroblast growth factors to mouse embryonic eye basement membranes.
Exp. Cell Res
171
,
63
75
Kostyk
S. K.
,
Wheeler
E. L.
,
Wagner
J. A.
(
1996
)
Unusual expression of the HU paraneoplastic antigen in the visual system.
Neuro Report
7
,
1549
1552
Liu
I. S. C.
,
Chen
J.
,
Ploder
L.
,
Vidgen
D.
,
van der Kooy
D.
,
Kalnis
V. I.
,
McInnes
R. R.
(
1994
)
Developmental expression of a novel murine homeobox gene (Chx10): Evidence for roles in determination of the neuroretina and inner nuclear layer.
Neuron
13
,
377
393
Marusich
M. F.
,
Furneaux
H. M.
,
Henion
P. D.
,
Weston
J. A.
(
1993
)
Hu neuronal proteins are expressed in proliferating neurogenic cells.
J. Neurobiology
25
,
143
155
Mathers
P. H.
,
Grinberg
A.
,
Mahon
K. A.
,
Jamrich
M.
(
1997
)
The Rx homeobox gene is essential for vertebrate eye development.
Nature
387
,
603
607
McAvoy
J. W.
,
Chamberlain
C. G.
(
1990
)
Growth factors in the eye.
Prog. Growth Factor Res
2
,
29
43
McFarlane
S.
,
Cornel
E.
,
Amaya
E.
,
Holt
C. E.
(
1996
)
Inhibition of FGF receptor activity in retinal.
Neuron
17
,
245
254
McLoon
S. C.
,
Barnes
R. B.
(
1989
)
Early differentiation of retinal ganglion cells: An axonal protein expressed by premigratory and migrating retinal ganglion cells.
J. Neuroscience
9
,
1424
1432
Mikawa
T.
(
1995
)
Retroviral targeting of FGF and FGFR in cardiomyocytes and coronary vasculogensis: Discontinuous formation of coronary vessels.
Ann. NY Acad. Sci
752
,
506
516
Monaghan
A. P.
,
Davidson
D. R.
,
Sime
C.
,
Graham
E.
,
Baldock
R.
,
Bhattacharya
S. S.
,
Hill
R. E.
(
1991
)
The Msh-like homeobox genes define domains inthe developing vertebrate eye.
Development
112
,
1053
1061
Nornes
H. O.
,
Dressler
G. R.
,
Knapik
E. W.
,
Deutsch
U.
,
Gruss
P.
(
1990
)
Spatially and temporally restricted expression ofPax2 during murine neurogenesis.
Development
109
,
797
809
Oliver
G.
,
Mailhos
A.
,
Wehr
R.
,
Copeland
N. G.
,
Jankins
N. A.
,
Gruss
P.
(
1995
)
Six3, a murine homologues ofthe sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development.
Development
121
,
4045
4055
Orts-Llorca
F.
,
Genis-Galvez
J. M.
(
1960
)
Experimental production of retinal septs in the chick embryo. Differentiation of pigment epithelium into neural retina.
Acta Anat
42
,
3170
–.
Park
C. M.
,
Hollenberg
M. J.
(
1989
)
Basic FGF growth factor induces retinal regeneration in vivo.
Dev. Biol
134
,
201
205
Park
C. M.
,
Hollenberg
M. J.
(
1991
)
Induction of retinal regeneration in vivo by growth factors.
Dev. Biol
148
,
322
333
Pittack
C. B.
,
Grunwald
G. B.
,
Reh
T. A.
(
1997
)
Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos.
Development
124
,
805
816
Reh
T. A.
(
1992
)
Cellular interactions determine neuronal phenotypes in rodent retinal cultures.
J. Neurobiology
23
,
1067
1083
Rydel
R. E.
,
Greene
L. A.
(
1987
)
Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells.
J. Neuroscience
7
,
3639
3653
Sparrow
J. R.
,
Hicks
D.
,
Barnstable
C. J.
(
1990
)
Cell commitment and differentiation in explants of embryonic rat neural retina. Comparison with the developmental potential of dissociated retina.
Dev. Brain Res
51
,
69
84
Stroeva
O. G.
(
1960
)
Experimental analysis of the eye morphogenesis in mammals.
J. Embryol. Exp. Morph
8
,
349
368
Tcheng
M.
,
Fuhrman
G.
,
Hartman
M.-P.
,
Courtois
Y.
,
Jeanny
J.-C.
(
1994
)
Spatial and temporal expression patterns of FGF receptor genes type 1 and type 2 in the developing chick retina.
Exp. Eye Res
58
,
352
358
Togari
A.
,
Dickens
G.
,
Kazuya
H.
,
Guroff
G.
(
1985
)
The effect of fibroblast growth factor on PC12 cells.
J. Neurosci
5
,
307
316
Wanaka
A.
,
Milbrand
J.
,
Johnson
E. M.
Jr.
(
1991
)
Expression of FGF receptor gene in rat development.
Development
111
,
455
468
Watanabe
T.
,
Raff
M. C.
(
1992
)
Diffusible rod-promoting signal in the developing rat retina.
Development
114
,
899
906
Yang
Y.
,
Niswander
L.
(
1995
)
Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: Dorsal signals regulate anteroposterior patterning.
Cell
80
,
939
947
Zhao
S.
,
Thornquist
S. C.
,
Barnstable
C. J.
(
1995
)
In vitro transdifferentiation of embryonic rat retinal pigment epithelium to neural retina.
Brain Res
677
,
300
310
Zhao
S.
,
Rizzolo
L. J.
,
Barnstable
C. J.
(
1997
)
Differentiation and transdifferentiation of the retinal pigment epithelium.
Inter. Rev. Cytology
171
,
225
266
This content is only available via PDF.