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Gli/Zic factors pattern the neural plate by defining domains of cell differentiation

Nature volume 393, pages 579–583 (1998)Cite this article

Abstract

Three cell types differentiate in the early frog neural plate: neural crest at the lateral edges, floorplate at the midline and primary neurons in three bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic hedgehog1,2 (Shh) and neural crest and dorsal neurons are induced by epidermal factors such as bone morphogenetic proteins (BMPs)3. Neurogenesis in a subset of cells within the stripes involves lateral inhibition4. However, the process by which pools of precursors are defined in stereotypic domains in response to inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger transcription factor of the Gli superfamily which is expressed in stripes that alternate with those in which primary neurons differentiate and overlap the domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis and induces neural crest differentiation. Conversely, Gli proteins are widely expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest-inducing functions that counteract the neurogenic but not the floorplate-inducing activity of Gli proteins. We propose that the combined function of Gli/Zic genes responds to inductive signals and induces patterned neural cell differentiation.

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Figure 1: Neural expression of Zic2 in frog embryos.
Figure 2: Effects of Zic2 and VP16–Zic2 on neurogenesis.
Figure 3: Induction of neurogenesis by Glis and repression by EnR–Gli2 and Zic2.
Figure 4: Neural crest induction by Zic2 and repression by VP16–Zic2 and Gli2.

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References

  1. Roelink, H.et al. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Cell 76, 761–775 (1995).

    Article  Google Scholar 

  2. Ruiz i Altaba, A., Jessell, T. M. & Roelink, H. Restrictions to floor plate induction by hedgehog and winged-helix genes in the neural tube of frog embryos. Mol. Cell. Neurosci. 6, 106–121 (1995).

    Article  CAS  Google Scholar 

  3. Liem, K. F. J, Tremml, G., Roelink, H. & Jessell, T. M. Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82, 969–979 (1995).

    Article  CAS  Google Scholar 

  4. Chitnis, A., Henrique, D., Lewis, J., Ish-Horowicz, D. & Kintner, C. Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature 375, 761–766 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Aruga, J.et al. The mouse Zic gene family, J. Biol. chem. 271, 1043–1047 (1996).

    Article  CAS  Google Scholar 

  6. Nagai, T.et al. The expression of the mouse Zic1, Zic2 and Zic3 genes suggests an essential role for Zic genes in body pattern formation. Dev. Biol. 182, 299–313 (1997).

    Article  CAS  Google Scholar 

  7. Aruga, J.et al. Anovel zinc finger protein, Zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells. J. Neurochem. 63, 1880–1890 (1994).

    Article  CAS  Google Scholar 

  8. Ma, Q., Kintner, C. & Anderson, D. J. Identification of Ngnr1, a vertebrate neuronal determination gene. Cell 87, 43–52 (1996).

    Article  CAS  Google Scholar 

  9. Ferreiro, B., Kintner, C., Zimmerman, K., Anderson, D. & Harris, W. A. XASH genes promote neurogenesis in Xenopus embryos. Development 20, 3649–3655 (1994).

    Google Scholar 

  10. Han, K. & Manley, J. L. Functional domains of the Drosophila engrailed protein. EMBO J. 12, 2723–2733 (1993).

    Article  CAS  Google Scholar 

  11. Kinzler, K. W. & Vogelstein, B. The Gli gene encodes a nuclear protein which binds specific sequences in the human genome. Mol. Cell. Biol. 10, 634–642 (1990).

    Article  CAS  Google Scholar 

  12. Lee, J., Platt, K. A., Censullo, P. & Ruiz i Altaba, A. Gli1 is a target of sonic hedgehog that induces ventral neural tube development. Development 124, 2537–2552 (1997).

    CAS  PubMed  Google Scholar 

  13. Marine, J.-C., Bellefroid, E. J., Pendeville, H., Martial, J. A. & Pieler, T. Arole for Xenopus Gli-type zinc finger proteins in the early embryonic patterning of mesoderm and neuroectoderm. Mech. Dev. 63, 211–225 (1997).

    Article  Google Scholar 

  14. Ruiz i Altaba, A. Cooperation of planar and vertical signals in the induction and patterning of the Xenopus nervous system. Development 115, 67–80 (1992).

    Google Scholar 

  15. Mayor, R., Morgan, R. & Sargent, M. Induction of the prospective neural crest in Xenopus. Development 121, 767–777 (1995).

    CAS  PubMed  Google Scholar 

  16. Essex, L. J., Mayor, R. & Sargent, M. G. Expression of Xenopus Snail in mesoderm and prospective neural fold ectoderm. Dev. Dynam. 198, 108–122 (1993).

    Article  CAS  Google Scholar 

  17. Ruiz i Altaba, A. & Théry, C. Involvement of Livertine, a hepatocyte growth factor family member, in neural morphogenesis. Mech. Dev. 60, 207–220 (1996).

    Article  CAS  Google Scholar 

  18. Mizuseki, K., Kishi, M., Matsui, M., Nakanishi, S. & Sasai, Y. Xenopus Zic-related-1 and Sox2, two factors induced by chordin, have distinct activities in the initiation of neural induction. Development 125, 579–587 (1998).

    CAS  PubMed  Google Scholar 

  19. Nakata, K., Nagai, T., Aruga, J. & Mikoshiba, K. Xenopus Zic3, a primary regulator both in neural and neural crest development. Proc. Natl Acad. Sci. USA 94, 11980–11985 (1997).

    Article  ADS  CAS  Google Scholar 

  20. Ruiz i Altaba, A. Catching a Gli-mpse of hedgehog. Cell 90, 193–196 (1997).

    Article  Google Scholar 

  21. Baker, N. E. & Yu, S.-Y. Proneural function of neurogenic genes in the developing Drosophila eye. Curr. Biol. 7, 122–132 (1997).

    Article  CAS  Google Scholar 

  22. Ishibashi, M.et al. Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev. 9, 3136–3148 (1995).

    Article  CAS  Google Scholar 

  23. Gans, C. & Northcutt, R. G. Neural crest and the origin of vertebrates: A new head. Science 220, 268–274 (1983).

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank G. Fishell, R. Lehmann, M. Belvin, W. Talbot, N. Dahmane, A. Schier and M. Van Doren for comments; K. Zimmerman for Pax3; Q. Ma and D. Anderson for Ngnr1; D. Turner for the pCS2 series; D. Kessler for pCS2-EnR; D. Melton for NCAM; and J. Aruga and H. Sive for discussion. This work was supported by Skirball Institute start-up funds, a Basil O'Connor Award from the March of Dimes a Pew Fellowship and a grant from the NIH to A.R.A.

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  1. Department of Cell Biology, The Skirball Institute, Developmental Genetics Program, NYU Medical Center, 540 First Avenue, New York, 10016, New York, USA

    R. Brewster, J. Lee & A. Ruiz i Altaba

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  1. R. Brewster
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Correspondence to A. Ruiz i Altaba.

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Brewster, R., Lee, J. & Altaba, A. Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature 393, 579–583 (1998). https://doi.org/10.1038/31242

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