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The role of neuroD as a differentiation factor in the mammalian retina

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Abstract

NeuroD, a vertebrate homolog of Drosophila atonal gene, plays an important role in the differentiation of neuronal precursors (Lee et al., 1995). We have investigated whether NeuroD subserves a similar function in mammalian retinal neurogenesis. Expression of NeuroD is detected in successive stages of retinal neurogenesis and is associated with a differentiating population of retinal cells. The association of NeuroD predominantly with postmitotic precursors in early as well as late neurogenesis suggests that NeuroD expression plays an important role in the terminal differentiation of retinal neurons. This notion is supported by observations that overexpression of NeuroD during late neurogenesis promotes premature differentiation of late-born neurons, rod photoreceptors, and bipolar cells, and that NeuroD can interact specifically with the E-box element in the proximal promoter of the phenotype-specific gene, opsin.

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References

  • Acharya H. R., Dooley C. M., Thoreson W. B., and Ahmad I. (1997) cDNA cloning and expression analysis of NeuroD mRNA in human retina. Biochem. Biophys. Res. Commun. 233, 459–463.

    Article  PubMed  CAS  Google Scholar 

  • Ahmad I. (1995) Mash-1 is expressed during rod photoreceptor differentiation and binds an E-box element in the opsin promoter. Dev. Brain Res. 90, 184–189.

    Article  CAS  Google Scholar 

  • Ahmad I. (1996) Involvement of NeuroD, bHLH factor in the vertebrate retinal development. Soc. Neurosci. Abst. 27, 504.

    Google Scholar 

  • Ahmad I., Dooley C. M., and Polk D. (1997) Delta-1 is a regulator of neurogenesis in the vertebrate retina. Dev. Biol. 185, 92–103.

    Article  PubMed  CAS  Google Scholar 

  • Ahmad I., Dooley C. M., and Afiat S. (1998) Involvement of Mash 1 in EGF mediated regulation of differentiation in the vertebrate retina. Dev. Biol. 194, 86–98.

    Article  PubMed  CAS  Google Scholar 

  • Ahmad I., Zagouras P., and Artavanis-Tsakonas S. (1995) Involvement of Notch-1 in mammalian retinal neurogenesis, association of Notch-1 expression with successive cell-fate determination and differentiated phenotypes. Mech. Dev. 53, 73–85.

    Article  PubMed  CAS  Google Scholar 

  • Altshuler D. and Cepko C. (1992) A temporally regulated difussible activity is required for rod photoreceptor development in vitro. Development 114, 947–957.

    PubMed  CAS  Google Scholar 

  • Altshuler D., Turner D. L., and Cepko C. (1990) Determination of cell fate during retinal histogenesis, in Development of the Visual System (Lam D. M. and Shatz C. J., eds.), MIT Press, Cambridge, MA, pp. 37–58.

    Google Scholar 

  • Anchan R. M., Reh T. A., Angello J., Balliet A., and Walker M. (1991) EGF and TGFa stimulate retinal neuroepithelial cell proliferation in vitro. Neuron 6, 923–936.

    Article  PubMed  CAS  Google Scholar 

  • Artavanis-Tsakonas S., Matsuno K., and Fortini M. (1995) Notch signaling. Science 268, 225–232.

    Article  PubMed  CAS  Google Scholar 

  • Austin C. P., Feldman D. E., Ida J. A., and Cepko C. L. (1995) Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch. Development 121, 3637–3650.

    PubMed  CAS  Google Scholar 

  • Bahnson A. B., Dunigan J. T., Baysal B. E., Mohney T., Atchison R. W., Nimgaonkar M. T., Ball E. D., and Barranger J. A. (1995) Centrifugal enhancement of retroviral mediated gene transfer. J. Virol. Meth. 54, 131–143.

    Article  CAS  Google Scholar 

  • Banerjee U. and Zpursky S. L. (1990) The role of cell-cell interaction in the development of Drosophila visual system. Neuron 4, 177–187.

    Article  PubMed  CAS  Google Scholar 

  • Barnstable C. J. (1980) Monoclonal antibodies which recognize different cell types in the rat retina. Nature 286, 231–235.

    Article  PubMed  CAS  Google Scholar 

  • Briggs S. D., Sharkey M., Stevenson M., and Smithgall T. E. (1997) SH3 mediated HcK tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1. J. Biol. Chem. 272, 17,899–17,902.

    Article  CAS  Google Scholar 

  • Cabrera C. V. (1992) The generation of cell diversity during early neurogenesis in Drosophila. Development 115, 893–901.

    PubMed  CAS  Google Scholar 

  • Carter-Dawson L. D. and La Vail M. M. (1979) Rods and cones in the mouse retina-II. Autoradiographic analysis of cell generation using tritiated thymidine. J. Comp. Neurol. 188, 263–272.

    Article  PubMed  CAS  Google Scholar 

  • Cau E., Gradwohl G., Fode C., and Guillemot F. (1997) Mash-1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124, 1611–1621.

    PubMed  CAS  Google Scholar 

  • Chen S., Wang Q-L., Nie Z., Sun H., Lennon G., Copeland N. G., Gilbert D. J., Jenkins N. A., and Zack D. J. (1997) Crx, a novel otx-like paired homeo domain protein, binds to and transactivates photo-receptor cell-specific genes. Neuron 19, 1017–1030.

    Article  PubMed  CAS  Google Scholar 

  • Chitnis A. and Kintner C. (1996) Sensitivity of proneural genes to lateral inhibition affects the primary neurons in Xenopus embryo. Development 122, 2295–2301.

    PubMed  CAS  Google Scholar 

  • Christie G. A. (1964) Developmental stages in somite and post-somite rat embryos. Based on external appearance, and including some features of the macroscopic development of the oral cavity. J. Morphol. 114, 263–286.

    Article  PubMed  CAS  Google Scholar 

  • de la Pompa J. L., Wakeham A., Correia E., Samper E., Brown S., Aguilera R. J., et al. (1997) Conservation of Notch signalling pathway in mammalian neurogenesis. Development 124, 1139–1148.

    PubMed  Google Scholar 

  • Di Polo A. and Farber D. B. (1995) Rod photoreceptor-specific gene expression in human retinoblastoma cells. Proc. Natl. Acad. Sci. USA 92, 4016–4020.

    Article  PubMed  Google Scholar 

  • Dorsky R. I., Chang S. W., Rapaport D. H., and Harris W. A. (1997) Regulation of neuronal diversity in the Xenopus retina by Delta signaling. Nature 385, 67–70.

    Article  PubMed  CAS  Google Scholar 

  • Freund C., Horsford J., and Roderick R. I. (1996) Transcription factor genes and developing eye, a genetic perspective. Human Mol. Genet. 5, 1471–1488.

    CAS  Google Scholar 

  • Furukawa T., Morrow E. M., and Cepko C. L. (1997) Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 91, 531–541.

    Article  PubMed  CAS  Google Scholar 

  • Greferath U., Grunert U., and Wassle H. (1990) Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. J. Comp. Neurol. 301, 433–442.

    Article  PubMed  CAS  Google Scholar 

  • Guillemot F., Lo L., Johnson J. E., Auerbach A., Anderson D. J., and Joyner A. L. (1993) Mammalian achaete scute homolog 1 is required for an early development of olfactory and autonomic neurons. Cell 75, 463–476.

    Article  PubMed  CAS  Google Scholar 

  • Kanekar S., Perron M., Dorsky R., Harris W. A., Jan L. Y., Jan Y. N., and Vetter M. L. (1997) Xath5 participates in a network of bHLH genes in the developing Xenopus retina. Neuron 19, 981–994.

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi T., Raju K., Breitman M. L., and Shinohara T. (1993) The proximal promoter of the mouse arrestin gene directs gene expression in photore-ceptor cells and contains an evolutionary conserved retina-factor binding sites. Mol. Cell Biol. 13, 4400–4408.

    PubMed  CAS  Google Scholar 

  • Kumar R., Schiming C., Scheurer D., Wang Q. L., Duh E., Sung C.-H., et al. (1996) The bZIP transcription factor Nrl stimulates rhodopsin promoter activity in primary retinal cell cultures. J. Biol. Chem. 271, 29,612–29,618.

    CAS  Google Scholar 

  • La Vail M. M., Rapaport H. H., and Rakic P. (1991) Cytogenesis in the monkey retina. J. Comp. Neurol. 309, 86–114.

    Article  PubMed  Google Scholar 

  • Lee J. E., Hollenberg S. M., Snider L., Turner J. L., Lipnick N., and Weintraub H. (1995) Conversation of Xenopus ectoderm into neurons by Neuro D, a basic helix-loop helix-protein. Science 268, 836–844.

    Article  PubMed  CAS  Google Scholar 

  • Lenardo M., Pierce J. W., and Baltimore D. (1987) Protein binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science 236, 1573–1577.

    Article  PubMed  CAS  Google Scholar 

  • Li J. and Smithgall T. E. (1998) Fibroblast transformation by Fps/Fes tyrosine kinase requires Ras, Rac and cDc42 and induces ERK nad JNK activation. J. Biol. Chem. 273, 13,828–13,834.

    CAS  Google Scholar 

  • Lillien L. (1995) Changes in retinal cell fate induced by overexpression of EGF receptor. Nature 377, 158–162.

    Article  PubMed  CAS  Google Scholar 

  • Ma Q., Kintner C., and Anderson D. J. (1996) Identification of neurogenin, a vertebrate neuronal determination gene. Cell 87, 43–52.

    Article  PubMed  CAS  Google Scholar 

  • Morabito M. A., Yu X., and Barnstable C. J. (1991) Characterization of developmentally regulated and retina-specific nuclear protein binding to a site in the upstream region of the rat opsin gene. J. Biol. Chem. 266, 9667–9672.

    PubMed  CAS  Google Scholar 

  • Muller A. J., Young J. C., Pendergast A. M., Pondel M., Landau N. R., Littman D. R., and Witte O. N. (1991) BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogne of philadelphia chromosome positive human leukemias. Mol. Cell. Biol. 11, 1785–1792.

    PubMed  CAS  Google Scholar 

  • Parada C., Puga J., Perez-Mendez L., Lopez R., and Ramirez G. (1991) Spatial and temporal patterns of neurogenesis in the chick retina. Eur. J. Neurosci. 3, 559–569.

    Article  Google Scholar 

  • Perron M., Kanekar S., Vetter M. L., and Harris W. A. (1998) The genetic sequence of retinal development in the ciliary margin of the Xenopus eye. Dev. Biol. 199, 185–200.

    Article  PubMed  CAS  Google Scholar 

  • Rawls A. and Olson E. N. (1997) MyoD meets its maker. Cell 89, 5–8.

    Article  PubMed  CAS  Google Scholar 

  • Reh T. A. (1992) Cellular interactions determine neuronal phenotypes in rodent retinal cultures. J. Neurobiol. 23, 1067–1083.

    Article  PubMed  CAS  Google Scholar 

  • Rehemtulla A., Warwar R., Kumar R., Jl X., Zack D. J., and Swaroop A. (1996) The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. Proc. Natl. Acad. Sci. USA 93, 191–195.

    Article  PubMed  CAS  Google Scholar 

  • Roztocil T., Matter-Sadzinski L., Alliod C., Ballivet M., and Matter J.-M. (1997) NeuroM, a neural helix-loop-helix transcription factor, defines a new transition stage in neurogenesis. Development 124, 3263–3272.

    PubMed  CAS  Google Scholar 

  • Sidman R. L. (1961) Histogenesis of mouse retina studied with thymidine 3H, in The Structure of the Eye (Smelser G., ed.), Academic, New York, pp. 487–506.

    Google Scholar 

  • Simpson P. (1995) Positive and negative regulators of neural fate. Neuron 15, 739–742.

    Article  PubMed  CAS  Google Scholar 

  • Sommer L., Ma Q., and Anderson D. J. (1996) Neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination gene that reveal progenitor cell heterogeneity is the developing CNS and PNS. Mol. Cell Neurosci. 8, 221–241.

    Article  PubMed  CAS  Google Scholar 

  • Sparrow J. R., Hicks D., and Barnstable C. J. (1990) Cell commitment and differentiation in explants of embryonic retina. Comparison with developmental potential of dissociated retina. Dev. Brain Res. 51, 69–84.

    Article  CAS  Google Scholar 

  • Swaroop A., Xu J., Pawar H., Jackson A., Skolnick A., and Agarwal N. (1992) A conserved reina-specific gene encodes a basic motif/leucine zipper domain. Proc. Natl. Acad. Sci. USA 89, 266–270.

    Article  PubMed  CAS  Google Scholar 

  • Takebayoshi K., Takahasi S., Yokota C., Tsuda H., Nakanishi S., Asashima M., and Kagryama R. (1997) Conversion of ectoderm into neural fate by ATH-3 a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal. EMBO J. 16, 384–395.

    Article  Google Scholar 

  • Tomita K., Nakanishi S., Guillemot I., and Kagyama R. (1996) Mash1 promotes neuronal differentiation in the retina. Genes Cells 7, 765–774.

    Article  Google Scholar 

  • Treisman J. E., Morabito M. A., and Barnstable C. J. (1988) Opsin expression in rat retina is regulated by transcriptional activation. Mol. Cell. Biol. 8, 1570–1579.

    PubMed  CAS  Google Scholar 

  • Turner D. L. and Weintraub H. (1994) Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate. Genes Dev. 8, 1434–1447.

    PubMed  CAS  Google Scholar 

  • Watanabe T. and Raff M. C. (1990) Rod photoreceptor development in vitro, intrinsic properties of proliferating neuroephithelial cells change as development proceeds in the rat retina. Neuron 4, 461–467.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T. and Raff M. C. (1992) Diffusiable rodpromoting signals in the developing rat retina. Development 116, 931–941.

    Google Scholar 

  • Young R. W. (1985) Cell differentiation in the retina of the mouse. Anat. Rec. 212, 199–205.

    Article  PubMed  CAS  Google Scholar 

  • Yu X., Chung M., Morabito M. A., and Barnstable C. J. (1993) Shared nuclear protein binding sites in the upstream region of the rat opsin gene. Biochem. Biophys. Res. Com. 191, 76–82.

    Article  PubMed  CAS  Google Scholar 

  • Zhao S. and Barnstable C. J. (1995) Differential effects of bFGF on development of rat retina. Brain Res. 723, 169–176.

    Article  Google Scholar 

  • Zimmerman K., Shih J., Bars J., Collazo A., and Anderson D. J. (1993) Xash-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along mediolateral axis of the neural plate. Development 119, 221–232.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, University of Nebraska Medical Center, 68198-6395, Omaha, NE

    Iqbal Ahmad, Harsha R. Acharya, Jim A. Rogers & Constance M. Dooley

  2. The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 68198-6395, Omaha, NE

    Iqbal Ahmad, Annemarie Shibata & Thomas E. Smithgall

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  1. Iqbal Ahmad
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  2. Harsha R. Acharya
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  3. Jim A. Rogers
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Ahmad, I., Acharya, H.R., Rogers, J.A. et al. The role of neuroD as a differentiation factor in the mammalian retina. J Mol Neurosci 11, 165–178 (1998). https://doi.org/10.1385/JMN:11:2:165

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