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Gene Review

lft1  -  lefty1

Danio rerio

Synonyms: SO:0000704, antivin, atv, cb73, ik:tdsubc_2b12, ...
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High impact information on lft1

  • 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 [1].
  • Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes [1].
  • The lefty-related factor Xatv acts as a feedback inhibitor of nodal signaling in mesoderm induction and L-R axis development in xenopus [2].
  • Our data also provide insights into the way that lefty/nodal signals interact in the initiation of differential L-R morphogenesis [2].
  • Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain [3].

Biological context of lft1

  • Here, we report that flounder and two fugu species, Takifugu and Tetraodon, have a single lefty gene in their genomes [4].
  • We infer that the lefty genes of the ray-finned fishes and mammals underwent independent gene duplication events that resulted in independent regulation of lefty expression [4].
  • The lefty gene encodes a member of the TGF-beta superfamily that regulates L-R axis formation during embryogenesis via antagonistic activity against Nodal, another TGF-beta superfamily member [4].
  • In addition, we provide evidence that the mouse lefty genes were duplicated on a single chromosome but the zebrafish lefty genes arose from a whole-genome duplication that occurred early in the divergence of ray-finned fishes [4].
  • We present three lines of evidence that Lefty proteins diminish the range of Squint signaling by acting not only as antagonists of Squint autoregulation but also as long-range inhibitors of Squint activity [5].

Anatomical context of lft1

  • In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development [3].
  • Asymmetric expression of antivin/lefty1 in the early chick embryo [6].

Regulatory relationships of lft1

  • Overexpression of dkk1 promoted anterior neuroectoderm development in the embryos injected with antivin RNA, which lack most of the mesoderm and endoderm, suggesting that Dkk1 can affect regionalization of neuroectoderm independently of dorso-anterior mesendoderm [7].

Other interactions of lft1

  • Furthermore, we find that Cyclops is specifically required for the maintenance of lefty1 and lefty2 transcription [8].
  • The normally left-sided Nodal signal spaw as well as its inhibitor lefty are expressed bilaterally, while pitx2 may appear random or bilateral [9].


  1. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo. Thisse, B., Wright, C.V., Thisse, C. Nature (2000) [Pubmed]
  2. The lefty-related factor Xatv acts as a feedback inhibitor of nodal signaling in mesoderm induction and L-R axis development in xenopus. Cheng, A.M., Thisse, B., Thisse, C., Wright, C.V. Development (2000) [Pubmed]
  3. Regulation of midline development by antagonism of lefty and nodal signaling. Bisgrove, B.W., Essner, J.J., Yost, H.J. Development (1999) [Pubmed]
  4. Flounder and fugu have a single lefty gene that covers the functions of lefty1 and lefty2 of zebrafish during L-R patterning. Hashimoto, H., Uji, S., Kurokawa, T., Washio, Y., Suzuki, T. Gene (2007) [Pubmed]
  5. Lefty proteins are long-range inhibitors of squint-mediated nodal signaling. Chen, Y., Schier, A.F. Curr. Biol. (2002) [Pubmed]
  6. Asymmetric expression of antivin/lefty1 in the early chick embryo. Ishimaru, Y., Yoshioka, H., Tao, H., Thisse, B., Thisse, C., V E Wright, C., Hamada, H., Ohuchi, H., Noji, S. Mech. Dev. (2000) [Pubmed]
  7. Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Hashimoto, H., Itoh, M., Yamanaka, Y., Yamashita, S., Shimizu, T., Solnica-Krezel, L., Hibi, M., Hirano, T. Dev. Biol. (2000) [Pubmed]
  8. 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]
  9. A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left-right asymmetry downstream or in parallel to nodal flow. Ellertsdottir, E., Ganz, J., Dürr, K., Loges, N., Biemar, F., Seifert, F., Ettl, A.K., Kramer-Zucker, A.K., Nitschke, R., Driever, W. Dev. Dyn. (2006) [Pubmed]
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