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Gene Review

ndr1  -  nodal-related 1

Danio rerio

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High impact information on ndr1

  • 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 [1].
  • We propose that modulation of intercellular signalling by Antivin/Activin and Nodal-related factors provides a mechanism for the graded establishment of cell fates along the antero-posterior axis of the zebrafish embryo [2].
  • Misexpression of sqt RNA within the embryo or specifically in the YSL induces expanded or ectopic dorsal mesoderm [3].
  • The sqt gene is expressed in a dorsal region of the blastula that includes the extraembryonic yolk syncytial layer (YSL) [3].
  • Here we report that the zebrafish squint (sqt) and cyclops (cyc) genes have essential, although partly redundant, functions in organizer development and also in the formation of mesoderm and endoderm [3].

Biological context of ndr1

  • During somitogenesis, ndr2 is expressed asymmetrically in the lateral plate as are nodal-related genes of other organisms, and in a small domain in the left diencephalon, providing the first observation of asymmetric gene expression in the embryonic forebrain [4].
  • Third, boz;sqt double mutants have a much more severe phenotype than boz and sqt single mutants [5].
  • The mechanism of sqt RNA transport was examined using cytoskeletal inhibitors [6].
  • Here, we describe the localization of transcripts encoding the nodal-related morphogen, Squint (sqt), in zebrafish oocytes and early embryos, and the mechanisms by which sqt RNA is localized. sqt transcripts are uniformly distributed in oocytes through all stages of oogenesis [6].
  • Localization of sqt transcripts is independent of maternal Wnt pathway function and requires a highly conserved sequence in the 3' untranslated region [7].

Anatomical context of ndr1

  • Ndr1 is expressed maternally, and ndr1 and ndr2 are expressed during blastula stage in the blastoderm margin [4].
  • We suggest that Ndr1 has a role in mesoderm induction, while Ndr2 is involved in subsequent specification and patterning of the nervous system and establishment of laterality [4].
  • We describe the isolation and characterization of zebrafish nodal-related 2 (znr2). znr2 is expressed at low levels maternally, and zygotic transcripts localize to dorsal blastomeres at MBT [8].
  • During gastrulation, ndr expression subdivides the shield into two domains: a small group of noninvoluting cells, the dorsal forerunner cells, express ndr1, while ndr2 RNA is found in the hypoblast layer of the shield and later in notochord, prechordal plate, and overlying anterior neurectoderm [4].
  • The zygotic expression of boz and sqt in the dorsal blastoderm and dorsal yolk syncytial layer (YSL) was dependent on the maternally derived Wnt signal, and their expression at the late blastula and early gastrula stages was dependent on the zygotic expression of their own genes [9].

Associations of ndr1 with chemical compounds


Regulatory relationships of ndr1

  • Our data imply that the Nodal related signal Cyc induces shh expression in the ventral neural tube [10].

Other interactions of ndr1

  • Abnormal dorsal patterning can first be observed at 3.5 hpf by the lack of nuclear accumulation of (beta)-catenin in the dorsal yolk syncytial layer, which also fails to express bozozok/dharma/nieuwkoid and znr2/ndr1/squint [11].
  • Functional comparison of Znr2 and another recently identified zebrafish nodal-related factor, Znr1/Cyclops, reveals distinct inductive properties of each ligand [8].
  • Furthermore, Znr2 overexpression exclusively in the YSL, a region implicated in endogenous mesodermal induction, causes broadened or duplicated gsc expression in the overlying blastoderm [8].
  • Expression of chordin and noggin1 is greatly reduced in boz;sqt mutants, indicating that the boz and sqt pathways have overlapping roles in activating secreted BMP antagonists [5].
  • Morpholino phenocopies of sqt, oep, and ntl mutations [12].

Analytical, diagnostic and therapeutic context of ndr1


  1. The zebrafish Nodal signal Squint functions as a morphogen. Chen, Y., Schier, A.F. Nature (2001) [Pubmed]
  2. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo. Thisse, B., Wright, C.V., Thisse, C. Nature (2000) [Pubmed]
  3. Zebrafish organizer development and germ-layer formation require nodal-related signals. Feldman, B., Gates, M.A., Egan, E.S., Dougan, S.T., Rennebeck, G., Sirotkin, H.I., Schier, A.F., Talbot, W.S. Nature (1998) [Pubmed]
  4. Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry. Rebagliati, M.R., Toyama, R., Fricke, C., Haffter, P., Dawid, I.B. Dev. Biol. (1998) [Pubmed]
  5. bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish. Sirotkin, H.I., Dougan, S.T., Schier, A.F., Talbot, W.S. Development (2000) [Pubmed]
  6. Localization of transcripts of the zebrafish morphogen Squint is dependent on egg activation and the microtubule cytoskeleton. Gore, A.V., Sampath, K. Mech. Dev. (2002) [Pubmed]
  7. The zebrafish dorsal axis is apparent at the four-cell stage. Gore, A.V., Maegawa, S., Cheong, A., Gilligan, P.C., Weinberg, E.S., Sampath, K. Nature (2005) [Pubmed]
  8. 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]
  9. Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the formation of the dorsal organizer in zebrafish. Shimizu, T., Yamanaka, Y., Ryu, S.L., Hashimoto, H., Yabe, T., Hirata, T., Bae, Y.K., Hibi, M., Hirano, T. Mech. Dev. (2000) [Pubmed]
  10. Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS. Müller, F., Albert, S., Blader, P., Fischer, N., Hallonet, M., Strähle, U. Development (2000) [Pubmed]
  11. Maternally controlled (beta)-catenin-mediated signaling is required for organizer formation in the zebrafish. Kelly, C., Chin, A.J., Leatherman, J.L., Kozlowski, D.J., Weinberg, E.S. Development (2000) [Pubmed]
  12. Morpholino phenocopies of sqt, oep, and ntl mutations. Feldman, B., Stemple, D.L. Genesis (2001) [Pubmed]
  13. 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]
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