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Gene Review

Lefty2  -  left-right determination factor 2

Mus musculus

Synonyms: 6030463A22Rik, AV214969, Ebaf, Left-right determination factor 2, Left-right determination factor B, ...
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High impact information on Lefty2

  • The lack of lefty-1 resulted in bilateral expression of nodal, lefty-2, and Pitx2 (a homeobox gene normally expressed on the left side) [1].
  • These observations suggest that the role of lefty-1 is to restrict the expression of lefty-2 and nodal to the left side, and that lefty-2 or nodal encodes a signal for "leftness."[1]
  • Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer [2].
  • These results suggest that similar transcriptional mechanisms underlie the asymmetric expression of nodal and of lefty-2 as well as the earlier expression of nodal in the epiblast and endoderm [2].
  • These duplications are preceded by ectopic expression of Foxa2, an axial mesoderm gene involved in node specification, with a concomitant reduction in Lefty2, a marker for lateral mesoderm [3].

Biological context of Lefty2

  • The mutant mice failed to express Nodal, Lefty2 and Pitx2 on the left side during embryogenesis and exhibited right isomerism [4].
  • RESULTS: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome [5].
  • These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos [5].
  • Conversely, ectopic expression of the Nodal inhibitor Lefty2 in the node of Nodal(neo/+) embryos resulted in a phenotype similar to that of the Nodal(neo/neo) mutant [6].
  • Nodal gene expression in the node was initiated in cryptic mutant mice, but neither nodal, lefty-2 nor Pitx2 were expressed in the left lateral plate mesoderm [7].

Anatomical context of Lefty2

  • In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction [5].
  • Ebaf/lefty participates in tissue remodelling of human endometrium by induction of matrix metalloproteases (MMP) [8].
  • No expression of the TGF-beta family member lefty-2 is observed in any foxj1(-/-) early somite stage embryos [9].

Other interactions of Lefty2

  • However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning defects [10].
  • Here we show additionally that left-sided expression of pitx2 and lefty-2 are also perturbed in Furin-deficient embryos [11].


  1. lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H., Hamada, H. Cell (1998) [Pubmed]
  2. Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. Adachi, H., Saijoh, Y., Mochida, K., Ohishi, S., Hashiguchi, H., Hirao, A., Hamada, H. Genes Dev. (1999) [Pubmed]
  3. Tcf3: a transcriptional regulator of axis induction in the early embryo. Merrill, B.J., Pasolli, H.A., Polak, L., Rendl, M., García-García, M.J., Anderson, K.V., Fuchs, E. Development (2004) [Pubmed]
  4. Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate. Yamamoto, M., Mine, N., Mochida, K., Sakai, Y., Saijoh, Y., Meno, C., Hamada, H. Development (2003) [Pubmed]
  5. Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Meno, C., Ito, Y., Saijoh, Y., Matsuda, Y., Tashiro, K., Kuhara, S., Hamada, H. Genes Cells (1997) [Pubmed]
  6. Left-right patterning of the mouse lateral plate requires nodal produced in the node. Saijoh, Y., Oki, S., Ohishi, S., Hamada, H. Dev. Biol. (2003) [Pubmed]
  7. A role of the cryptic gene in the correct establishment of the left-right axis. Gaio, U., Schweickert, A., Fischer, A., Garratt, A.N., Müller, T., Ozcelik, C., Lankes, W., Strehle, M., Britsch, S., Blum, M., Birchmeier, C. Curr. Biol. (1999) [Pubmed]
  8. Lefty is expressed in mouse endometrium in estrous cycle and peri-implantation period. Tang, M., Xu, Y., Julian, J., Carson, D., Tabibzadeh, S. Hum. Reprod. (2005) [Pubmed]
  9. Foxj1 regulates asymmetric gene expression during left-right axis patterning in mice. Zhang, M., Bolfing, M.F., Knowles, H.J., Karnes, H., Hackett, B.P. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Norris, D.P., Brennan, J., Bikoff, E.K., Robertson, E.J. Development (2002) [Pubmed]
  11. Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping. Constam, D.B., Robertson, E.J. Development (2000) [Pubmed]
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