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Gene Review

ndr2  -  nodal-related 2

Danio rerio

Synonyms: Ndr-2, SO:0000704, Znr-1, cyc, cyclops, ...
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High impact information on ndr2

  • An identical phenotype is displayed by double mutants for the nodal-related genes squint and cyclops [1].
  • Here we test the morphogen properties of Cyclops and Squint-two Nodal-related transforming growth factor-beta signals required for mesoderm formation and patterning in zebrafish [2].
  • 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 cyc, a mutation of a conserved cysteine in the mature ligand [3].
  • The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system [4].
  • Moreover, ectopic expression of PKI partially rescues somite and optic stalk defects in no tail and cyclops mutants that lack midline structures that normally synthesize Shh [5].

Biological context of ndr2


Anatomical context of ndr2

  • In double mutants for the zebrafish nodal-related genes squint (sqt) and cyclops (cyc) [3] [4] [5], dorsal marginal cells adopt neural fates, whereas in wild-type embryos, cells at this position form endoderm and axial mesoderm [10].
  • In contrast, while Znr1/Cyclops reproducibly induces mesodermal and neural markers, it is an inefficient inducer of organizer-type mesoderm [11].
  • In addition, zebrafish fast is also expressed bilaterally in the dorsal diencephalon, where the nodal-related cyclops gene is only expressed on the left side [12].
  • The nodal-related genes cyclops and squint are expressed at the blastoderm margin and are required for prechordal plate and notochord formation [13].
  • The first gene, crestin, is expressed predominantly in premigratory and migrating neural crest cells during somitogenesis stages. crestin expression is reduced in cyc mutants initially but recovers by late somitogenesis [8].

Associations of ndr2 with chemical compounds

  • Zebrafish crestin was identified in a screen for genes dependent on cyclops function and is a member of a family of retroelements (Rubinstein et al. [2000] Genesis 26:86-97) [14].
  • Inhibition of the endoplasmic reticulum Ca(2+) pump during early gastrulation induces cyclopia, mimicking defects observed in cyclops, squint, one-eyed pinhead, and silberblick mutant embryos [15].

Regulatory relationships of ndr2


Other interactions of ndr2

  • Overexpression of truncated smad2 in cyclops mutant embryos leads to a rescue of the eye and floorplate defects [18].
  • Furthermore, we find that Cyclops is specifically required for the maintenance of lefty1 and lefty2 transcription [19].
  • In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5 [20].
  • In zebrafish, mesoderm and endoderm formation requires the Nodal signals Cyclops and Squint and their cofactor One-eyed pinhead (Oep) [10-14] [21].
  • Zebrafish calreticulin is highly expressed in the hatching gland and in the floor plate, tissues that are affected in cyc mutants [8].

Analytical, diagnostic and therapeutic context of ndr2


  1. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Gritsman, K., Zhang, J., Cheng, S., Heckscher, E., Talbot, W.S., Schier, A.F. Cell (1999) [Pubmed]
  2. The zebrafish Nodal signal Squint functions as a morphogen. Chen, Y., Schier, A.F. Nature (2001) [Pubmed]
  3. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Sampath, K., Rubinstein, A.L., Cheng, A.M., Liang, J.O., Fekany, K., Solnica-Krezel, L., Korzh, V., Halpern, M.E., Wright, C.V. Nature (1998) [Pubmed]
  4. The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system. Hatta, K., Kimmel, C.B., Ho, R.K., Walker, C. Nature (1991) [Pubmed]
  5. Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Hammerschmidt, M., Bitgood, M.J., McMahon, A.P. Genes Dev. (1996) [Pubmed]
  6. The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm. Dougan, S.T., Warga, R.M., Kane, D.A., Schier, A.F., Talbot, W.S. Development (2003) [Pubmed]
  7. One-eyed pinhead regulates cell motility independent of Squint/Cyclops signaling. Warga, R.M., Kane, D.A. Dev. Biol. (2003) [Pubmed]
  8. Genes dependent on zebrafish cyclops function identified by AFLP differential gene expression screen. Rubinstein, A.L., Lee, D., Luo, R., Henion, P.D., Halpern, M.E. Genesis (2000) [Pubmed]
  9. A floor plate enhancer of the zebrafish netrin1 gene requires Cyclops (Nodal) signalling and the winged helix transcription factor FoxA2. Rastegar, S., Albert, S., Le Roux, I., Fischer, N., Blader, P., Müller, F., Strähle, U. Dev. Biol. (2002) [Pubmed]
  10. Nodal-related signals establish mesendodermal fate and trunk neural identity in zebrafish. Feldman, B., Dougan, S.T., Schier, A.F., Talbot, W.S. Curr. Biol. (2000) [Pubmed]
  11. Zebrafish nodal-related 2 encodes an early mesendodermal inducer signaling from the extraembryonic yolk syncytial layer. Erter, C.E., Solnica-Krezel, L., Wright, C.V. Dev. Biol. (1998) [Pubmed]
  12. Cloning and expression pattern of a zebrafish homolog of forkhead activin signal transducer (FAST), a transcription factor mediating Nodal-related signals. Boggetti, B., Argenton, F., Haffter, P., Bianchi, M.E., Cotelli, F., Beltrame, M. Mech. Dev. (2000) [Pubmed]
  13. Nodal signaling patterns the organizer. Gritsman, K., Talbot, W.S., Schier, A.F. Development (2000) [Pubmed]
  14. Specific pan-neural crest expression of zebrafish Crestin throughout embryonic development. Luo, R., An, M., Arduini, B.L., Henion, P.D. Dev. Dyn. (2001) [Pubmed]
  15. The calcium pump of the endoplasmic reticulum plays a role in midline signaling during early zebrafish development. Creton, R. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  16. A temperature-sensitive mutation in the nodal-related gene cyclops reveals that the floor plate is induced during gastrulation in zebrafish. Tian, J., Yam, C., Balasundaram, G., Wang, H., Gore, A., Sampath, K. Development (2003) [Pubmed]
  17. Expression of a type II collagen gene in the zebrafish embryonic axis. Yan, Y.L., Hatta, K., Riggleman, B., Postlethwait, J.H. Dev. Dyn. (1995) [Pubmed]
  18. Cloning and characterization of zebrafish smad2, smad3 and smad4. Dick, A., Mayr, T., Bauer, H., Meier, A., Hammerschmidt, M. Gene (2000) [Pubmed]
  19. Lefty antagonism of Squint is essential for normal gastrulation. Feldman, B., Concha, M.L., Saúde, L., Parsons, M.J., Adams, R.J., Wilson, S.W., Stemple, D.L. Curr. Biol. (2002) [Pubmed]
  20. Induction of the mesendoderm in the zebrafish germ ring by yolk cell-derived TGF-beta family signals and discrimination of mesoderm and endoderm by FGF. Rodaway, A., Takeda, H., Koshida, S., Broadbent, J., Price, B., Smith, J.C., Patient, R., Holder, N. Development (1999) [Pubmed]
  21. Single-cell internalization during zebrafish gastrulation. Carmany-Rampey, A., Schier, A.F. Curr. Biol. (2001) [Pubmed]
  22. A class of neuroD-related basic helix-loop-helix transcription factors expressed in developing central nervous system in zebrafish. Liao, J., He, J., Yan, T., Korzh, V., Gong, Z. DNA Cell Biol. (1999) [Pubmed]
  23. Dynamic expression pattern of Nodal-related genes during left-right development in medaka. Soroldoni, D., Bajoghli, B., Aghaallaei, N., Czerny, T. Gene Expr. Patterns (2007) [Pubmed]
  24. Tenascin-C expression in the trunk of wild-type, cyclops and floating head zebrafish embryos. Tongiorgi, E. Brain Res. Bull. (1999) [Pubmed]
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