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Gene Review

Lefty1  -  left right determination factor 1

Mus musculus

Synonyms: AI450052, Ebaf, Left-right determination factor 1, Leftb, Lefty, ...
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Disease relevance of Lefty1


High impact information on Lefty1

  • 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."[5]
  • Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant, indicating that inv may act early in left/right determination [6].
  • Lefty protein contains the cysteine-knot motif characteristic of this superfamily and is secreted as a processed form of relative molecular mass 25K-32K [7].
  • In vertebrates, specification of anteroposterior (A/P) and left-right (L/R) axes depends on TGFbeta-related signals, including Nodal, Lefty, and BMPs [8].
  • In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS) [9].

Biological context of Lefty1

  • 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 [10].
  • RESULTS: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome [10].
  • The mutation of the consensus sequences for PC cleavage in the lefty protein allowed the lefty cleavage sites to be identified [11].
  • Recently, we showed that, during undisturbed estrous cycle, lefty is present in mouse uterine horn primarily in a precursor form [12].
  • Taken together, the findings show that decidualized differentiation of stroma, which is a prerequisite for embryo implantation, leads to processing of lefty by PC5/6A [12].

Anatomical context of Lefty1


Associations of Lefty1 with chemical compounds


Regulatory relationships of Lefty1

  • Ectopic Nodal expression in right LPM also induced Lefty1 expression in the floor plate [17].
  • Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1 [15].

Other interactions of Lefty1

  • Left-right asymmetric signaling molecules in mammals include three transforming growth factor beta (TGFbeta)-related factors, Nodal, Lefty1 and Lefty2 [18].
  • TGFbeta-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination [10].
  • This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene [13].
  • Nodal signaling thus initiates asymmetric Nodal expression in LPM and induces Lefty1 at the midline [17].
  • However loss of the ASE disrupts Lefty2 (Leftb) expression and causes delayed Pitx2 expression leading to late onset, relatively minor LR patterning defects [19].

Analytical, diagnostic and therapeutic context of Lefty1


  1. The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function in the establishment of handedness. Heymer, J., Kuehn, M., Rüther, U. Mech. Dev. (1997) [Pubmed]
  2. Stra3/lefty, a retinoic acid-inducible novel member of the transforming growth factor-beta superfamily. Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Mattei, M.G., Dollé, P., Chambon, P. Int. J. Dev. Biol. (1998) [Pubmed]
  3. Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model. Mason, J.M., Xu, H.P., Rao, S.K., Leask, A., Barcia, M., Shan, J., Stephenson, R., Tabibzadeh, S. J. Biol. Chem. (2002) [Pubmed]
  4. In vivo gene transfer of lefty leads to implantation failure in mice. Tang, M., Taylor, H.S., Tabibzadeh, S. Hum. Reprod. (2005) [Pubmed]
  5. 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]
  6. Cloning of inv, a gene that controls left/right asymmetry and kidney development. Mochizuki, T., Saijoh, Y., Tsuchiya, K., Shirayoshi, Y., Takai, S., Taya, C., Yonekawa, H., Yamada, K., Nihei, H., Nakatsuji, N., Overbeek, P.A., Hamada, H., Yokoyama, T. Nature (1998) [Pubmed]
  7. Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos. Meno, C., Saijoh, Y., Fujii, H., Ikeda, M., Yokoyama, T., Yokoyama, M., Toyoda, Y., Hamada, H. Nature (1996) [Pubmed]
  8. SPC4/PACE4 regulates a TGFbeta signaling network during axis formation. Constam, D.B., Robertson, E.J. Genes Dev. (2000) [Pubmed]
  9. Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. Saijoh, Y., Adachi, H., Mochida, K., Ohishi, S., Hirao, A., Hamada, H. Genes Dev. (1999) [Pubmed]
  10. 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]
  11. Lefty proteins exhibit unique processing and activate the MAPK pathway. Ulloa, L., Creemers, J.W., Roy, S., Liu, S., Mason, J., Tabibzadeh, S. J. Biol. Chem. (2001) [Pubmed]
  12. Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing. Tang, M., Mikhailik, A., Pauli, I., Giudice, L.C., Fazelabas, A.T., Tulac, S., Carson, D.D., Kaufman, D.G., Barbier, C., Creemers, J.W., Tabibzadeh, S. Endocrinology (2005) [Pubmed]
  13. Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Perea-Gomez, A., Vella, F.D., Shawlot, W., Oulad-Abdelghani, M., Chazaud, C., Meno, C., Pfister, V., Chen, L., Robertson, E., Hamada, H., Behringer, R.R., Ang, S.L. Dev. Cell (2002) [Pubmed]
  14. The mouse embryo autonomously acquires anterior-posterior polarity at implantation. Takaoka, K., Yamamoto, M., Shiratori, H., Meno, C., Rossant, J., Saijoh, Y., Hamada, H. Dev. Cell (2006) [Pubmed]
  15. Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Tsukui, T., Capdevila, J., Tamura, K., Ruiz-Lozano, P., Rodriguez-Esteban, C., Yonei-Tamura, S., Magallón, J., Chandraratna, R.A., Chien, K., Blumberg, B., Evans, R.M., Belmonte, J.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  16. Coordinate expression of novel genes during osteoblast differentiation. Seth, A., Lee, B.K., Qi, S., Vary, C.P. J. Bone Miner. Res. (2000) [Pubmed]
  17. 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]
  18. Role of asymmetric signals in left-right patterning in the mouse. Hamada, H., Meno, C., Saijoh, Y., Adachi, H., Yashiro, K., Sakuma, R., Shiratori, H. Am. J. Med. Genet. (2001) [Pubmed]
  19. 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]
  20. 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]
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