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Proc Natl Acad Sci U S A. Jan 23, 1996; 93(2): 589–595.

Cell fate determination in the vertebrate retina.


In the vertebrate central nervous system, the retina has been a useful model for studies of cell fate determination. Recent results from studies conducted in vitro and in vivo suggest a model of retinal development in which both the progenitor cells and the environment change over time. The model is based upon the notion that the mitotic cells within the retina change in their response properties, or "competence", during development. These changes presage the ordered appearance of distinct cell types during development and appear to be necessary for the production of the distinct cell types. As the response properties of the cells change, so too do the environmental signals that the cells encounter. Together, intrinsic properties and extrinsic cues direct the choice of cell fate.

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  • Martí E, Bumcrot DA, Takada R, McMahon AP. Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature. 1995 May 25;375(6529):322–325. [PubMed]
  • Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessell TM. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell. 1995 May 5;81(3):445–455. [PubMed]
  • Hynes M, Porter JA, Chiang C, Chang D, Tessier-Lavigne M, Beachy PA, Rosenthal A. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron. 1995 Jul;15(1):35–44. [PubMed]
  • Dräger UC, Olsen JF. Origins of crossed and uncrossed retinal projections in pigmented and albino mice. J Comp Neurol. 1980 Jun;191(3):383–412. [PubMed]
  • Young RW. Cell death during differentiation of the retina in the mouse. J Comp Neurol. 1984 Nov 1;229(3):362–373. [PubMed]
  • Young RW. Cell differentiation in the retina of the mouse. Anat Rec. 1985 Jun;212(2):199–205. [PubMed]
  • Cagan R. Cell fate specification in the developing Drosophila retina. Dev Suppl. 1993:19–28. [PubMed]
  • Tomlinson A, Ready DF. Neuronal differentiation in Drosophila ommatidium. Dev Biol. 1987 Apr;120(2):366–376. [PubMed]
  • Turner DL, Cepko CL. A common progenitor for neurons and glia persists in rat retina late in development. Nature. 1987 Jul 9;328(6126):131–136. [PubMed]
  • Turner DL, Snyder EY, Cepko CL. Lineage-independent determination of cell type in the embryonic mouse retina. Neuron. 1990 Jun;4(6):833–845. [PubMed]
  • Holt CE, Bertsch TW, Ellis HM, Harris WA. Cellular determination in the Xenopus retina is independent of lineage and birth date. Neuron. 1988 Mar;1(1):15–26. [PubMed]
  • Fekete DM, Perez-Miguelsanz J, Ryder EF, Cepko CL. Clonal analysis in the chicken retina reveals tangential dispersion of clonally related cells. Dev Biol. 1994 Dec;166(2):666–682. [PubMed]
  • Wetts R, Fraser SE. Multipotent precursors can give rise to all major cell types of the frog retina. Science. 1988 Mar 4;239(4844):1142–1145. [PubMed]
  • Adler R, Hatlee M. Plasticity and differentiation of embryonic retinal cells after terminal mitosis. Science. 1989 Jan 20;243(4889):391–393. [PubMed]
  • Altshuler D, Cepko C. A temporally regulated, diffusible activity is required for rod photoreceptor development in vitro. Development. 1992 Apr;114(4):947–957. [PubMed]
  • Lillien L, Cepko C. Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. Development. 1992 May;115(1):253–266. [PubMed]
  • Sparrow JR, Hicks D, Barnstable CJ. Cell commitment and differentiation in explants of embryonic rat neural retina. Comparison with the developmental potential of dissociated retina. Brain Res Dev Brain Res. 1990 Jan 1;51(1):69–84. [PubMed]
  • Mack AF, Fernald RD. Thin slices of teleost retina continue to grow in culture. J Neurosci Methods. 1991 Feb;36(2-3):195–202. [PubMed]
  • Reh TA. Cellular interactions determine neuronal phenotypes in rodent retinal cultures. J Neurobiol. 1992 Oct;23(8):1067–1083. [PubMed]
  • Treisman JE, Morabito MA, Barnstable CJ. Opsin expression in the rat retina is developmentally regulated by transcriptional activation. Mol Cell Biol. 1988 Apr;8(4):1570–1579. [PMC free article] [PubMed]
  • Watanabe T, Raff MC. Rod photoreceptor development in vitro: intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina. Neuron. 1990 Mar;4(3):461–467. [PubMed]
  • Altshuler D, Lo Turco JJ, Rush J, Cepko C. Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development. 1993 Dec;119(4):1317–1328. [PubMed]
  • Kelley MW, Turner JK, Reh TA. Retinoic acid promotes differentiation of photoreceptors in vitro. Development. 1994 Aug;120(8):2091–2102. [PubMed]
  • Waid DK, McLoon SC. Immediate differentiation of ganglion cells following mitosis in the developing retina. Neuron. 1995 Jan;14(1):117–124. [PubMed]
  • Barnstable CJ, Hofstein R, Akagawa K. A marker of early amacrine cell development in rat retina. Brain Res. 1985 Jun;352(2):286–290. [PubMed]
  • Lin LF, Mismer D, Lile JD, Armes LG, Butler ET, 3rd, Vannice JL, Collins F. Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). Science. 1989 Nov 24;246(4933):1023–1025. [PubMed]
  • Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ, Patterson PH. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989 Dec 15;246(4936):1412–1416. [PubMed]
  • Ip NY, McClain J, Barrezueta NX, Aldrich TH, Pan L, Li Y, Wiegand SJ, Friedman B, Davis S, Yancopoulos GD. The alpha component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development. Neuron. 1993 Jan;10(1):89–102. [PubMed]
  • Darnell JE, Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. [PubMed]
  • Schlessinger J, Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 1992 Sep;9(3):383–391. [PubMed]
  • Austin CP, Feldman DE, Ida JA, Jr, Cepko CL. Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch. Development. 1995 Nov;121(11):3637–3650. [PubMed]
  • Prada Carmen, Puga José, Pérez-Méndez Luisa, López Rosario, Ramírez Galo. Spatial and Temporal Patterns of Neurogenesis in the Chick Retina. Eur J Neurosci. 1991 Jun;3(6):559–569. [PubMed]
  • Artavanis-Tsakonas S, Matsuno K, Fortini ME. Notch signaling. Science. 1995 Apr 14;268(5208):225–232. [PubMed]
  • Henrique D, Adam J, Myat A, Chitnis A, Lewis J, Ish-Horowicz D. Expression of a Delta homologue in prospective neurons in the chick. Nature. 1995 Jun 29;375(6534):787–790. [PubMed]
  • Sechrist JW. Neurocytogenesis. I. Neurofibrils, neurofilaments, and the terminal mitotic cycle. Am J Anat. 1969 Jan;124(1):117–133. [PubMed]
  • Guillemot F, Cepko CL. Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development. Development. 1992 Mar;114(3):743–754. [PubMed]
  • Arimatsu Y, Naegele JR, Barnstable CJ. Molecular markers of neuronal subpopulations in layers 4, 5, and 6 of cat primary visual cortex. J Neurosci. 1987 Apr;7(4):1250–1263. [PubMed]
  • Inoue A, Obata K, Akagawa K. Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. J Biol Chem. 1992 May 25;267(15):10613–10619. [PubMed]
  • Bennett MK, Calakos N, Scheller RH. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 1992 Jul 10;257(5067):255–259. [PubMed]
  • Naegele JR, Barnstable CJ. A carbohydrate epitope defined by monoclonal antibody VC1.1 is found on N-CAM and other cell adhesion molecules. Brain Res. 1991 Sep 13;559(1):118–129. [PubMed]
  • Guillemot F, Joyner AL. Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. Mech Dev. 1993 Aug;42(3):171–185. [PubMed]
  • Jasoni CL, Walker MB, Morris MD, Reh TA. A chicken achaete-scute homolog (CASH-1) is expressed in a temporally and spatially discrete manner in the developing nervous system. Development. 1994 Apr;120(4):769–783. [PubMed]
  • Hernández-Sánchez C, Frade JM, de la Rosa EJ. Heterogeneity among neuroepithelial cells in the chick retina revealed by immunostaining with monoclonal antibody PM1. Eur J Neurosci. 1994 Jan 1;6(1):105–114. [PubMed]
  • Reh TA, Kljavin IJ. Age of differentiation determines rat retinal germinal cell phenotype: induction of differentiation by dissociation. J Neurosci. 1989 Dec;9(12):4179–4189. [PubMed]
  • Wassarman DA, Therrien M, Rubin GM. The Ras signaling pathway in Drosophila. Curr Opin Genet Dev. 1995 Feb;5(1):44–50. [PubMed]
  • Pawson T, Bernstein A. Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 1990 Nov;6(11):350–356. [PubMed]
  • O'Neill EM, Rebay I, Tjian R, Rubin GM. The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell. 1994 Jul 15;78(1):137–147. [PubMed]
  • Rebay I, Rubin GM. Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway. Cell. 1995 Jun 16;81(6):857–866. [PubMed]
  • Wasylyk B, Hahn SL, Giovane A. The Ets family of transcription factors. Eur J Biochem. 1993 Jan 15;211(1-2):7–18. [PubMed]
  • Dickson BJ, Domínguez M, van der Straten A, Hafen E. Control of Drosophila photoreceptor cell fates by phyllopod, a novel nuclear protein acting downstream of the Raf kinase. Cell. 1995 Feb 10;80(3):453–462. [PubMed]
  • Chang HC, Solomon NM, Wassarman DA, Karim FD, Therrien M, Rubin GM, Wolff T. phyllopod functions in the fate determination of a subset of photoreceptors in Drosophila. Cell. 1995 Feb 10;80(3):463–472. [PubMed]
  • Kimmel BE, Heberlein U, Rubin GM. The homeo domain protein rough is expressed in a subset of cells in the developing Drosophila eye where it can specify photoreceptor cell subtype. Genes Dev. 1990 May;4(5):712–727. [PubMed]
  • Basler K, Yen D, Tomlinson A, Hafen E. Reprogramming cell fate in the developing Drosophila retina: transformation of R7 cells by ectopic expression of rough. Genes Dev. 1990 May;4(5):728–739. [PubMed]

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