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Gene Review

NODAL  -  nodal growth differentiation factor

Homo sapiens

Synonyms: Nodal homolog
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Disease relevance of NODAL


High impact information on NODAL

  • In addition, Nodal signaling is dependent on coreceptors of the EGF-CFC family and antagonized by the Lefty and Cerberus families of secreted factors [6].
  • Additional modulators of Nodal signaling include convertases that regulate the generation of the mature signal, and factors such as Arkadia and DRAP1 that regulate the cellular responses to the signal [6].
  • TGFss signals belonging to the Nodal family set up the embryonic axes, induce mesoderm and endoderm, pattern the nervous system, and determine left-right asymmetry in vertebrates [6].
  • These studies demonstrate that Nodal signaling is modulated at almost every level to precisely orchestrate tissue patterning during vertebrate embryogenesis [6].
  • A component of the ARC/Mediator complex required for TGF beta/Nodal signalling [7].

Chemical compound and disease context of NODAL


Biological context of NODAL


Anatomical context of NODAL


Associations of NODAL with chemical compounds

  • In addition, Nodal and ALK7-ca decreased the number of proliferating cells as measured by bromodeoxyuridine assays [1].
  • Recently, we demonstrated that Nodal mRNA and several ALK7 transcripts are expressed in human placenta throughout pregnancy (Roberts, H. J., Hu, S., Qiu, Q., Leung, P. C. K., Cannigia, I., Gruslin, A., Tsang, B., and Peng, C. (2003) Biol. Reprod. 68, 1719-1726) [1].
  • In particular, we discuss the role of the Shh pathway in this process and on its interactions with the FGF, retinoic acid and Nodal pathways and other information cascades that modify its effects [17].
  • Erratum: Nodal Cooper-pair stabilized phase dynamics in granular d-wave superconductors [Phys. Rev. Lett. 92, 037004 (2004)] [18].

Regulatory relationships of NODAL

  • Taken together, these observations establish that Smad2/3 is activated in undifferentiated hESCs and required for the expression of genes controlling Nodal signaling [19].
  • Nodal and Nodal-related proteins activate the Activin-like signal pathway and play a key role in the formation of mesoderm and endoderm in vertebrate development [20].

Other interactions of NODAL

  • This study shows that nodal and the inhibitors of Nodal signaling, lefty-A and lefty-B, are down-regulated very early upon differentiation [19].
  • Moreover, there appears to be cross-talk between inhibition of GSK3, a hallmark of Wnt signaling and the Activin/Nodal pathway [19].
  • Recently, we have cloned four transcripts of human activin receptor-like kinase 7 (ALK7), a type I receptor for Nodal [12].
  • Using a luciferase reporter assay, we found that Cripto has activities consistent with its being a coreceptor for Nodal [11].
  • Taken together, this study demonstrates for the first time that Nodal, acting through ALK7 and Smad2/3, inhibits proliferation and induces apoptosis in human trophoblast cells [1].

Analytical, diagnostic and therapeutic context of NODAL

  • However, Cripto can also function as a secreted signaling factor in cell coculture assays, suggesting that it may also act as a coligand for Nodal [11].
  • RESULTS: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS [21].
  • More Extensive Nodal Dissection Improves Survival for Stages I to III of Colon Cancer: A Population-Based Study [22].
  • CONCLUSIONS: Nodal basin failure after lymphadenectomy in patients who underwent previous biopsy of a histologically positive SLN is primarily a function of aggressive locoregional disease rather than of contamination from previous surgery [23].
  • In regard to: Lee RJ, et al. Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy. Int J. Radiat oncol biol phys 2000;46:467-474 [24].


  1. Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells. Munir, S., Xu, G., Wu, Y., Yang, B., Lala, P.K., Peng, C. J. Biol. Chem. (2004) [Pubmed]
  2. Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Xu, G., Zhou, H., Wang, Q., Auersperg, N., Peng, C. Mol. Cancer Res. (2006) [Pubmed]
  3. Embryonic heart induction. Foley, A.C., Gupta, R.W., Guzzo, R.M., Korol, O., Mercola, M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  4. New therapeutic strategy for gastric carcinoma: a two-step evaluation of malignant potential from its molecular biologic and pathologic characteristics. Kuwahara, A., Katano, M., Nakamura, M., Fujimoto, K., Miyazaki, K., Mori, M., Morisaki, T. Journal of surgical oncology. (1999) [Pubmed]
  5. Melanoma pathogenesis and Nodal: a partial picture? Salomon, D.S. Nat. Med. (2006) [Pubmed]
  6. Nodal signaling in vertebrate development. Schier, A.F. Annu. Rev. Cell Dev. Biol. (2003) [Pubmed]
  7. A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Kato, Y., Habas, R., Katsuyama, Y., Näär, A.M., He, X. Nature (2002) [Pubmed]
  8. Incidence of Dual AV Node Physiology Following Termination of AV Nodal Reentrant Tachycardia by Adenosine-5'-Triphosphate: A Comparison with Drug Administration in Sinus Rhythm. Belhassen, B., Fish, R., Viskin, S., Glick, A., Glikson, M., Eldar, M. Indian pacing and electrophysiology journal [electronic resource]. (2003) [Pubmed]
  9. CER1 is a common target of WNT and NODAL signaling pathways in human embryonic stem cells. Katoh, M., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  10. Nicalin and its binding partner Nomo are novel Nodal signaling antagonists. Haffner, C., Frauli, M., Topp, S., Irmler, M., Hofmann, K., Regula, J.T., Bally-Cuif, L., Haass, C. EMBO J. (2004) [Pubmed]
  11. Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway. Yan, Y.T., Liu, J.J., Luo, Y., E, C., Haltiwanger, R.S., Abate-Shen, C., Shen, M.M. Mol. Cell. Biol. (2002) [Pubmed]
  12. Nodal induces apoptosis and inhibits proliferation in human epithelial ovarian cancer cells via activin receptor-like kinase 7. Xu, G., Zhong, Y., Munir, S., Yang, B.B., Tsang, B.K., Peng, C. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  13. TGF-beta superfamily signaling and left-right asymmetry. Whitman, M., Mercola, M. Sci. STKE (2001) [Pubmed]
  14. Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling. Poulain, M., Fürthauer, M., Thisse, B., Thisse, C., Lepage, T. Development (2006) [Pubmed]
  15. Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning. Mesnard, D., Guzman-Ayala, M., Constam, D.B. Development (2006) [Pubmed]
  16. BMP signaling positively regulates Nodal expression during left right specification in the chick embryo. Piedra, M.E., Ros, M.A. Development (2002) [Pubmed]
  17. Sonic hedgehog signaling in forebrain development and its interactions with pathways that modify its effects. Bertrand, N., Dahmane, N. Trends Cell Biol. (2006) [Pubmed]
  18. Erratum: Nodal Cooper-pair stabilized phase dynamics in granular d-wave superconductors [Phys. Rev. Lett. 92, 037004 (2004)]. Joglekar, Y.N., Castro Neto, A.H., Balatsky, A.V. Phys. Rev. Lett. (2005) [Pubmed]
  19. Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. Besser, D. J. Biol. Chem. (2004) [Pubmed]
  20. Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled. Onuma, Y., Takahashi, S., Haramoto, Y., Tanegashima, K., Yokota, C., Whitman, M., Asashima, M. Dev. Dyn. (2005) [Pubmed]
  21. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? Gill, S., Loprinzi, C.L., Sargent, D.J., Thomé, S.D., Alberts, S.R., Haller, D.G., Benedetti, J., Francini, G., Shepherd, L.E., Francois Seitz, J., Labianca, R., Chen, W., Cha, S.S., Heldebrant, M.P., Goldberg, R.M. J. Clin. Oncol. (2004) [Pubmed]
  22. More Extensive Nodal Dissection Improves Survival for Stages I to III of Colon Cancer: A Population-Based Study. Chen, S.L., Bilchik, A.J. Ann. Surg. (2006) [Pubmed]
  23. Regional nodal basin control is not compromised by previous sentinel lymph node biopsy in patients with melanoma. Gershenwald, J.E., Berman, R.S., Porter, G., Mansfield, P.F., Lee, J.E., Ross, M.I. Ann. Surg. Oncol. (2000) [Pubmed]
  24. In regard to: Lee RJ, et al. Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy. Int J. Radiat oncol biol phys 2000;46:467-474. Kretschmer, L., Neumann, C., Marsch, W.C. Int. J. Radiat. Oncol. Biol. Phys. (2000) [Pubmed]
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