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Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling

Abstract

Zebrafish cyclops (cyc) mutations cause deficiencies in the dorsal mesendoderm1,2 and ventral neural tube3,4, leading to neural defects and cyclopia5,6. Here we report that cyc encodes a transforming growth factor-β (TGF-β)-related intercellular signalling molecule that is similar to mouse nodal7. cyc is expressed in dorsal mesendoderm at gastrulation and in the prechordal plate until early somitogenesis. Expression reappears transiently in the left lateral-plate mesoderm, and in an unprecedented asymmetric pattern in the left forebrain. Injection of cyc RNA non-autonomously restores sonic hedgehog -expressing cells of the ventral brain and floorplate that are absent in cyc mutants, whereas inducing activities are abolished by cycm294, a mutation of a conserved cysteine in the mature ligand. Our results indicate that cyc provides an essential non-cell-autonomous signal at gastrulation, leading to induction of the floorplate and ventral brain.

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Figure 1: cyclops is a nodal -related gene.
Figure 2: cyc expression in wild-type and mutant zebrafish.
Figure 3: Cyc inducing activities.
Figure 4: cyc RNA rescues ventral neural tube of mutants.

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References

  1. Thisse, C., Thisse, B., Halpern, M. E. & Postlethwait, J. H. goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas. Dev. Biol. 164, 420–429 (1994).

    Article  CAS  Google Scholar 

  2. Warga, R. Origin and Specification of the Endoderm in the Zebrafish. Thesis, Univ. Tubingen(1996)).

    Google Scholar 

  3. Hatta, K., Kimmel, C. B., Ho, R. K. & Walker, C. The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system. Nature 350, 339–341 (1991).

    Article  ADS  CAS  Google Scholar 

  4. Hatta, K., Puschel, A. W. & Kimmel, C. B. Midline signaling in the primordium of the zebrafish anterior central nervous system. Proc. Natl Acad. Sci. USA 91, 2061–2065 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Hatta, K. Role of the floor plate in axonal patterning in the zebrafish CNS. Neuron 9, 629–642 (1992).

    Article  CAS  Google Scholar 

  6. Macdonald, R.et al. Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain. Neuron 13, 1039–1053 (1994).

    Article  CAS  Google Scholar 

  7. Varlet, I., Collignon, J., Norris, D. P. & Robertson, E. J. Nodal signaling and axis formation in the mouse. Cold Spring Har. Symp. Quant. Biol. LXII, 105–113 (1997).

    Google Scholar 

  8. Tanabe, Y. & Jessell, T. M. Diversity and pattern in the developing spinal cord. Science 274, 1115–1123 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Chiang, C.et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Pituello, F., Yamada, G. & Gruss, P. Activin A inhibits Pax-6 expression and perturbs cell differentiation in the developing spinal cord in vitro. Proc. Natl Acad. Sci. USA 92, 6952–6956 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Artinger, K. B. & Bronner-Fraser, M. Delayed formation of the floor plate after ablation of the avian notochord. Neuron 11, 1147–1161 (1993).

    Article  CAS  Google Scholar 

  12. Halpern, M. E.et al. Genetic interactions in zebrafish midline development. Dev. Biol. 187, 154–170 (1997).

    Article  CAS  Google Scholar 

  13. Krauss, S., Concordet, J. P. & Ingham, P. W. Afunctionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431–1444 (1993).

    Article  CAS  Google Scholar 

  14. Toyama, R., O'Connell, M. L., Wright, C. V. E., Kuehn, M. R. & Dawid, I. Nodal induces ectopic goosecoid and lim1 expression and axis duplication in zebrafish. Development 121, 383–391 (1995).

    CAS  Google Scholar 

  15. Varlet, I. & Robertson, E. J. Left-right asymmetry in vertebrates. Curr. Opin. Genet. Dev. 7, 519–523 (1997).

    Article  CAS  Google Scholar 

  16. Postlethwait, J. H.et al. Agenetic linkage map for the zebrafish. Science 264, 699–703 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Talbot, W. S.et al. Genetic analysis of chromosomal rearrangements in the cyclops region of the zebrafish genome. Genetics 148, 373–380 (1998).

    CAS  Google Scholar 

  18. Schier, A. F.et al. Mutations affecting the development of the embryonic zebrafish brain. Development 123, 165–178 (1996).

    CAS  Google Scholar 

  19. Kingsley, D. M. The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 8, 133–146 (1994).

    Article  CAS  Google Scholar 

  20. Mason, A. J. Functional analysis of cysteine residues of activin A. Mol. Endocrinol. 8, 325–332 (1994).

    CAS  Google Scholar 

  21. Ekker, S. C.et al. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr. Biol. 5, 944–955 (1995).

    Article  CAS  Google Scholar 

  22. Brand, M.et al. Mutations affecting development of the midline and general body shape during zebrafish embryogenesis. Development 123, 129–142 (1996).

    CAS  Google Scholar 

  23. Strahle, U.et al. one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes Funct. 1, 131–148 (1997).

    Article  CAS  Google Scholar 

  24. Zhang, J., Talbot, W. S. & Schier, A. F. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell 92, 241–251 (1998).

    Article  CAS  Google Scholar 

  25. Butler, A. B. & Hodos, W. (eds) Comparative Vertebrate Neuroanatomy: Evolution and Adaption (J. Wiley, New York, (1996)).

    Google Scholar 

  26. Chen, J.-N.et al. Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development 124, 4373–4382 (1997).

    CAS  Google Scholar 

  27. Pera, E. M. & Kessel, M. Patterning of the chick forebrain anlage by the prechordal plate. Development 124, 4153–4162 (1997).

    CAS  Google Scholar 

  28. Dale, J. K.et al. Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90, 257–269 (1997).

    Article  CAS  Google Scholar 

  29. Heisenberg, C. P. & Nusslein-Volhard, C. The function of silberblick in the positioning of the eye anlage in the zebrafish embryo. Dev. Biol. 184, 85–94 (1997).

    Article  CAS  Google Scholar 

  30. Knapik, E. W.et al. Amicrosatellite genetic linkage map for zebrafish. Nature Genet. 18, 338–343 (1998).

    Article  CAS  Google Scholar 

  31. Feldman, B.et al. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature(in the press).

  32. Rebagliati, M. R., Toyama, R., Fricke, C., Haffter, P. & Dawid, I. B. Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry. Dev. Biol. 199, 261–272 (1998).

    Article  CAS  Google Scholar 

  33. Rebagliati, M. R., Toyama, R., Haffter, P. & Dawid, I. B. cyclops encodes a nodal-related factor involved in midline signaling. Proc. Natl. Acad. Sci. USA 95, 9932–9937 (1998).

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank C.-M. Fan, B. Hogan, R. Warga and I. Dawid for discussion; W. Driever, E.Knapik, M.Fishman, C. B. Kimmel, S. Ekker, J. Campos-Ortega, D. Kimelman, D. Wilkinson, D. Turner and C.Nüsslein-Volhard for reagents or zebrafish; S. Fisher, A. Switalski, A. Chilcoat and L. Friedman for map panel DNA; and M. Macurak, A. Pinder, M. Sepanski, D. Lee, B. Cortez, A. Hennessey, M. Ray and K. L. Poon for technical assistance. K.S. and V.K. are supported by NSTB, Singapore; A.L.R., A.M.S.C. and J.O.L. by NIH Training Awards; L.S.K. by the NIH and March of Dimes Birth Defects Foundation; M.E.H. by NSF and the Pew Scholars Program; and C.V.E.W. by the NIH.

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Sampath, K., Rubinstein, A., Cheng, A. et al. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Nature 395, 185–189 (1998). https://doi.org/10.1038/26020

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