Advertisement
JOURNAL ARTICLES
A role for the fibroblast growth factor receptor in cell fate decisions in the developing vertebrate retina
S. McFarlane, M.E. Zuber, C.E. Holt
Development 1998 125: 3967-3975;

Summary

The mature vertebrate retina contains seven major cell types that develop from an apparently homogenous population of precursor cells. Clonal analyses have suggested that environmental influences play a major role in specifying retinal cell identity. Fibroblast growth factor-2 is present in the developing retina and regulates the survival, proliferation and differentiation of developing retinal cells in culture. Here we have tested whether fibroblast growth factor receptor signaling biases retinal cell fate decisions in vivo. Fibroblast growth factor receptors were inhibited in retinal precursors in Xenopus embryos by expressing a dominant negative form of the receptor, XFD. Dorsal animal blastomeres that give rise to the retina were injected with cDNA expression constructs for XFD and a control non-functional mutant receptor, D48, and the cell fates of transgene-expressing cells in the mature retina determined. Fibroblast growth factor receptor blockade results in almost a 50% loss of photoreceptors and amacrine cells, and a concurrent 3.5-fold increase in Muller glia, suggesting a shift towards a Muller cell fate in the absence of a fibroblast growth factor receptor signal. Inhibition of non-fibroblast-growth-factor-mediated receptor signaling with a third mutant receptor, HAVO, alters cell fate in an opposite manner. These results suggest that it is the balance of fibroblast growth factor and non-fibroblast growth factor ligand signals that influences retinal cell genesis.

REFERENCES

    1. Adamus G.,
    2. Zam Z. S.,
    3. Arendt A.,
    4. Palczewski K.,
    5. McDowell J. H.,
    6. Hargrave P. A.
    (1991) Anti-rhodopsin monoclonal antibodies of defined specificity: characterization and application. Vision Res 31, 17–31
    OpenUrlCrossRefPubMedWeb of Science
    1. Altshuler D.,
    2. Cepko C.
    (1992) A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro. Development 114, 947–957
    OpenUrlAbstract
    1. Amaya E.,
    2. Musci T. J.,
    3. Kirschner M. W.
    (1991) Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66, 257–270
    OpenUrlCrossRefPubMedWeb of Science
    1. Amaya E.,
    2. Stein P. A.,
    3. Musci T. J.,
    4. Kirschner M. W.
    (1993) FGF signalling in the early specification of mesoderm in Xenopus. Development 118, 477–487
    OpenUrlAbstract
    1. Bahr M.,
    2. Vanselow J.,
    3. Thanos S.
    (1989) Ability of adult rat ganglion cells to regrow axons in vitro can be influenced by fibroblast growth factor and gangliosides. Neurosci. Lett 96, 197–201
    OpenUrl
    1. Belecky-Adams T.,
    2. Cook B.,
    3. Adler R.
    (1996) Correlations between terminal mitosis and differentiated fate of retinal precursor cells in vivo andin vitro: analysis with the ‘window-labeling’ technique. Dev. Biol 178, 304–315
    OpenUrlCrossRefPubMedWeb of Science
    1. Bouvier M. M.,
    2. Mytilineou C.
    (1995) Basic fibroblast growth factor increases division and delays differentiation of dopamine precursors in vitro. J. Neurosci 15, 7141–7149
    OpenUrlAbstract
    1. Bugra K.,
    2. Olivier L.,
    3. Jacquemin E.,
    4. Laurent M.,
    5. Courtois Y.,
    6. Hicks D.
    (1993) Acidic fibroblast growth factor is expressed abundantly by photoreceptors within the developing and mature rat retina. Eur. J. Neurosci 6, 1586–1595
    1. Byers S.,
    2. Amaya E.,
    3. Munro S.,
    4. Blaschuk O.
    (1992) Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain A hemagglutinins: a role in protein-protein interactions?. Dev. Biol 152, 411–414
    OpenUrlCrossRefPubMed
    1. Campochiaro P. A.,
    2. Chang M.,
    3. Ohsato M.,
    4. Vinores S. A.,
    5. Nie Z.,
    6. Hjelmeland L.,
    7. Mansukhani A.,
    8. Basilico C.,
    9. Zack D. J.
    (1996) Retinal degeneration in transgenic mice with photoreceptor-specific expression of a dominant-negative fibroblast growth factor receptor. J. Neurosci 16, 1679–1688
    OpenUrlAbstract/FREE Full Text
    1. Consigli S. A.,
    2. Lyser K. M.,
    3. Joseph-Silverstein J.
    (1993) The temporal and spatial expression of basic fibroblast growth factor during ocular development in the chicken. Invest. Ophthalmol. Vis. Sci 34, 559–566
    OpenUrlAbstract/FREE Full Text
    1. de Longh R.,
    2. 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
    OpenUrlPubMedWeb of Science
    1. Deng C. X.,
    2. Wynshaw-Boris A.,
    3. Shen M. M.,
    4. Daugherty C.,
    5. Ornitz D. M.,
    6. Leder P.
    (1994) Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev 8, 3045–3057
    OpenUrlAbstract/FREE Full Text
    1. Doherty P.,
    2. Smith P.,
    3. Walsh F. S.
    (1996) Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors. Perspect. Dev. Neurobiol 4, 157–168
    OpenUrlPubMedWeb of Science
    1. Dorsky R. I.,
    2. Rapaport D. H.,
    3. Harris W. A.
    (1995) Xotch inhibits cell differentiation in the Xenopus retina. Neuron 14, 487–496
    OpenUrlCrossRefPubMedWeb of Science
    1. Dorsky R.I.,
    2. Chang W.S.,
    3. Rapaport D.H.,
    4. Harris W. A.
    (1997) Regulation of neuronal diversity in the Xenopus retina by Delta signalling. Nature 385, 67–70
    OpenUrlCrossRefPubMed
    1. Drager U. C.,
    2. Edwards D. L.,
    3. Barnstable C. J.
    (1984) Antibodies against filamentous components in discrete cell types of the mouse retina. J. Neurosci 4, 2025–2042
    OpenUrlAbstract
    1. Evan G. I.,
    2. Lewis G. K.,
    3. Ramsay G.,
    4. Bishop J. M.
    (1985) Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol. Cell. Biol 5, 3610–3616
    OpenUrlAbstract/FREE Full Text
    1. Friesel R.,
    2. Dawid I. B.
    (1991) cDNA cloning and developmental expression of fibroblast growth factor receptors from Xenopus laevis. Mol. Cell. Biol 11, 2481–2488
    OpenUrlAbstract/FREE Full Text
    1. Friesel R.,
    2. Brown S. A.
    (1992) Spatially restricted expression of fibroblast growth factor receptor-2 during Xenopus development. Development 116, 1051–1058
    OpenUrlAbstract/FREE Full Text
    1. Fuhrmann S.,
    2. Kirsch M.,
    3. Hofmann H. D.
    (1995) Ciliary neurotrophic factor promotes chick photoreceptor development in vitro. Development 121, 2695–2706
    OpenUrlAbstract
    1. Gao H.,
    2. Hollyfield J. G.
    (1995) Basic fibroblast growth factor in retinal development: differential levels of bFGF expression and content in normal and retinal degeneration (rd) mutant mice. Dev. Biol 169, 168–184
    OpenUrlCrossRefPubMedWeb of Science
    1. Guillemot F.,
    2. Cepko C. L.
    (1992) Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development. Development 114, 743–754
    OpenUrlAbstract
    1. Harris W. A.,
    2. Messersmith S. L.
    (1992) Two cellular inductions involved in photoreceptor determination in the Xenopus retina. Neuron 9, 357–372
    OpenUrlCrossRefPubMedWeb of Science
    1. Hicks D.,
    2. Courtois Y.
    (1992) Fibroblast growth factor stimulates photoreceptor differentiation in vitro. J. Neurosci 12, 2022–2033
    OpenUrlAbstract
    1. Holt C. E.,
    2. Bertsch T. W.,
    3. Ellis H. M.,
    4. Harris W. A.
    (1988) Cellular determination in the Xenopus retina is independent of lineage and birth date. Neuron 1, 15–26
    OpenUrlCrossRefPubMedWeb of Science
    1. Holt C. E.,
    2. Garlick N.,
    3. Cornel E.
    (1990) Lipofection of cDNAs in the embryonic vertebrate central nervous system. Neuron 4, 203–214
    OpenUrlCrossRefPubMedWeb of Science
    1. Holtfreter J.
    (1943) Properties and functions of the surface coat in amphibian embryos. J. Exp. Zool 93, 251–323
    OpenUrlCrossRefWeb of Science
    1. Huang S.,
    2. Moody S. A.
    (1993) The retinal fate of Xenopus cleavage stage progenitors is dependent upon blastomere position and competence: studies of normal and regulated clones. J. Neurosci 13, 3193–3210
    OpenUrlAbstract
    1. Kelley M. W.,
    2. Turner J. K.,
    3. Reh T. A.
    (1994) Retinoic acid promotes differentiation of photoreceptors in vitro. Development 120, 2091–2102
    OpenUrlAbstract
    1. Kelley M. W.,
    2. Turner J. K.,
    3. Reh T. A.
    (1995) Ligands of steroid/thyroid receptors induce cone photoreceptors in vertebrate retina. Development 121, 3777–3785
    OpenUrlAbstract
    1. Kinoshita N.,
    2. Minshull J.,
    3. Kirschner M. W.
    (1995) The identification of two novel ligands of the FGF receptor by a yeast screening method and their activity in Xenopus development. Cell 83, 621–630
    OpenUrlCrossRefPubMedWeb of Science
    1. Kintner C. R.,
    2. Melton D. A.
    (1987) Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. Development 99, 311–325
    OpenUrlAbstract
    1. La Vail M. M.,
    2. Rapaport D. H.,
    3. Rakic P.
    (1991) Cytogenesis in the monkey retina. J. Comp. Neurol 309, 86–114
    OpenUrlCrossRefPubMedWeb of Science
    1. Lillien L.,
    2. Cepko C.
    (1992) Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. Development 115, 253–266
    OpenUrlAbstract
    1. Lillien L.
    (1995) Changes in retinal cell fate induced by overexpression of EGF receptor. Nature 377, 158–162
    OpenUrlCrossRefPubMed
    1. Mack A. F.,
    2. Fernald R. D.
    (1993) Regulation of cell division and rod differentiation in the teleost retina. Brain Res. Dev. Brain Res 76, 183–187
    OpenUrlCrossRefPubMed
    1. Mascarelli F.,
    2. Tassin J.,
    3. Courtois Y.
    (1991) Effect of FGFs on adult bovine Muller cells: proliferation, binding and internalization. Growth Factors 4, 81–95
    OpenUrlCrossRefPubMed
    1. McFarlane S.,
    2. McNeill L.,
    3. Holt C. E.
    (1995) FGF signaling and target recognition in the developing Xenopus visual system. Neuron 15, 1017–1028
    OpenUrlCrossRefPubMedWeb of Science
    1. McFarlane S.,
    2. Cornel E.,
    3. Amaya E.,
    4. Holt C. E.
    (1996) Inhibition of FGF receptor activity in retinal ganglion cells causes errors in target recognition. Neuron 17, 245–254
    OpenUrlCrossRefPubMedWeb of Science
    1. Park C. M.,
    2. Hollenberg M. J.
    (1989) Basic fibroblast growth factor induces retinal regeneration in vivo. Dev. Biol 134, 201–205
    OpenUrlCrossRefPubMedWeb of Science
    1. Park C. M.,
    2. Hollenberg M. J.
    (1991) Induction of retinal regeneration in vivo by growth factors. Dev. Biol 148, 322–333
    OpenUrlCrossRefPubMedWeb of Science
    1. Patstone G.,
    2. Pasquale E. B.,
    3. Maher P. A.
    (1993) Different members of the fibroblast growth factor receptor family are specific to distinct cell types in the developing chicken embryo. Dev. Biol 155, 107–123
    OpenUrlCrossRefPubMedWeb of Science
    1. Pittack C.,
    2. Jones M.,
    3. Reh T. A.
    (1991) Basic fibroblast growth factor induces retinal pigment epithelium to generate neural retina in vitro. Development 113, 577–588
    OpenUrlAbstract
    1. Pittack C.,
    2. Grunwald G. B.,
    3. Reh T. A.
    (1997) Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos. Development 124, 805–816
    OpenUrlAbstract
    1. Reh T. A.
    (1992) Cellular interactions determine neuronal phenotypes in rodent retinal cultures. J. Neurobiol 23, 1067–1083
    OpenUrlCrossRefPubMedWeb of Science
    1. Reichenbach A.,
    2. Schnitzer J.,
    3. Friedrich A.,
    4. Knothe A. K.,
    5. Henke A.
    (1991) Development of the rabbit retina: II. Muller cells. J. Comp. Neurol 311, 33–44
    OpenUrlCrossRefPubMedWeb of Science
    1. Riehl R.,
    2. Johnson K.,
    3. Bradley R.,
    4. Grunwald G. B.,
    5. Cornel E.,
    6. Lilienbaum A.,
    7. Holt C. E.
    (1996) Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo. Neuron 17, 837–848
    OpenUrlCrossRefPubMedWeb of Science
    1. Riou J. F.,
    2. Clavilier L.,
    3. Boucaut J. C.
    (1996) Early regionalizedexpression of a novel Xenopus fibroblast growth factor receptor in neuroepithelium. Biochem. Biophys. Res. Commun 218, 198–204
    OpenUrlCrossRefPubMed
    1. Sakaguchi D. S.,
    2. Janick L. M.,
    3. Reh T. A.
    (1997) Basic fibroblast growth factor (FGF-2) induced transdifferentiation of retinal pigment epithelium: generation of retinal neurons and glia. Dev. Dyn 209, 387–398
    OpenUrlCrossRefPubMedWeb of Science
    1. Shiozaki C.,
    2. Tashiro K.,
    3. Asano-Miyoshi M.,
    4. Saigo K.,
    5. Emori Y.,
    6. Shiokawa K.
    (1995) Cloning of cDNA and genomic DNA encoding fibroblast growth factor receptor-4 of Xenopus laevis. Gene 152, 215–219
    OpenUrlCrossRefPubMed
    1. Sievers J.,
    2. Hausmann B.,
    3. Unsicker K.,
    4. Berry M.
    (1987) Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve. Neurosci. Lett 76, 157–162
    OpenUrlCrossRefPubMedWeb of Science
    1. Song J.,
    2. Slack J. M.
    (1994) Spatial and temporal expression of basic fibroblast growth factor (FGF-2) mRNA and protein in early Xenopus development. Mech. Dev 48, 141–151
    OpenUrlCrossRefPubMedWeb of Science
    1. Song J.,
    2. Slack J. M.
    (1996) XFGF-9: a new fibroblast growth factor from Xenopus embryos. Dev. Dyn 206, 427–436
    OpenUrlCrossRefPubMedWeb of Science
    1. Tannahill D.,
    2. Isaacs H. V.,
    3. Close M. J.,
    4. Peters G.,
    5. Slack J. M.
    (1992) Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction. Development 115, 695–702
    OpenUrlAbstract/FREE Full Text
    1. Tcheng M.,
    2. Oliver L.,
    3. Courtois Y.,
    4. Jeanny J. C.
    (1994) Effects of exogenous FGFs on growth, differentiation, and survival of chick neural retina cells. Exp. Cell. Res 212, 30–35
    OpenUrlCrossRefPubMed
    1. Turner D. L.,
    2. Cepko C. L.
    (1987) A common progenitor for neurons and glia persists in rat retina late in development. Nature 328, 131–136
    OpenUrlCrossRefPubMedWeb of Science
    1. Turner D. L.,
    2. Snyder E. Y.,
    3. Cepko C. L.
    (1990) Lineage-independent determination of cell type in the embryonic mouse retina. Neuron 4, 833–845
    OpenUrlCrossRefPubMedWeb of Science
    1. Ueno H.,
    2. Gunn M.,
    3. Dell K.,
    4. Tseng A., Jr.,
    5. Williams L.
    (1992) A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor. J. Biol. Chem 267, 1470–1476
    OpenUrlAbstract/FREE Full Text
    1. Waid D. K.,
    2. McLoon S. C.
    (1995) Immediate differentiation of ganglion cells following mitosis in the developing retina. Neuron 14, 117–124
    OpenUrlCrossRefPubMedWeb of Science
    1. Wanaka A.,
    2. Milbrandt J.,
    3. Johnson E. J.
    (1991) Expression of FGF receptor gene in rat development. Development 111, 455–468
    OpenUrlAbstract
    1. Wetts R.,
    2. Fraser S. E.
    (1988) Multipotent precursors can give rise to all major cell types of the frog retina. Science 239, 1142–1145
    OpenUrlAbstract/FREE Full Text
    1. Williams E. J.,
    2. Furness J.,
    3. Walsh F. S.,
    4. Doherty P.
    (1994) Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. Neuron 13, 583–594
    OpenUrlCrossRefPubMedWeb of Science
    1. Yamaguchi T. P.,
    2. Harpal K.,
    3. Henkemeyer M.,
    4. Rossant J.
    (1994) fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. Genes Dev 8, 3032–3044
    OpenUrlAbstract/FREE Full Text
    1. Zhao S.,
    2. Barnstable C. J.
    (1996) Differential effects of bFGF on development of the rat retina. Brain Res 723, 169–176
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
A role for the fibroblast growth factor receptor in cell fate decisions in the developing vertebrate retina
S. McFarlane, M.E. Zuber, C.E. Holt
Development 1998 125: 3967-3975;
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

The people behind the papers – George Britton and Aryeh Warmflash

George and Aryeh

First author George Britton and his supervisor Aryeh Warmflash discuss their new Development paper in which they apply advanced in vitro culturing techniques to investigate embryonic ectoderm patterning.

Travelling Fellowship – New imaging approach unveils a bigger picture

Highlights from Travelling Fellowship trips

Find out how Pamela Imperadore’s Travelling Fellowship grant from The Company of Biologists took her to Germany, where she used new imaging techniques to investigate the cellular machinery underlying octopus arm regeneration. Don’t miss the next application deadline for 2020 travel, coming up on 29 November. Where will your research take you?

Protein function can be controlled by light using optogenetic techniques. In their new Primer, Stefano De Renzis and his colleagues in Heidelberg provide an overview of the most commonly used optogenetic tools and their application in developmental biology.

preLights – Self-organised symmetry breaking in zebrafish reveals feedback from morphogenesis to pattern formation

Sundar Naganathan

preLighter Sundar Naganathan explains his selected preprint by Vikas Trivedi, Benjamin Steventon and their co-workers on pescoids, a new in vitro model system to study early zebrafish embryogenesis.

Spotlight – Can laboratory model systems instruct human limb regeneration?

An extract from a schematic demonstrating the possible pipeline for how discovery in lab model systems can influence applications for regenerative therapies.

One of the most challenging objectives of tissue regeneration research is regrowth of a lost or amputated limb. Here, Ben Cox, Maximina Yun and Kenneth Poss outline the research avenues yet to be explored to move closer to this capstone achievement.

Articles of interest in our sister journals

Tox4 modulates cell fate reprogramming

Lotte Vanheer, Juan Song, Natalie De Geest, Adrian Janiszewski, Irene Talon, Caterina Provenzano, Taeho Oh, Joel Chappell, Vincent Pasque
Journal of Cell Science

Drosophila melanogaster: a simple system for understanding complexity

Stephanie E. Mohr, Norbert Perrimon
Disease Models & Mechanisms