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Gene Review

LEFTY1  -  left-right determination factor 1

Homo sapiens

Synonyms: LEFTB, LEFTYB, Left-right determination factor 1, Left-right determination factor B, Protein lefty-1, ...
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Disease relevance of LEFTY1


High impact information on LEFTY1

  • In addition, Nodal signaling is dependent on coreceptors of the EGF-CFC family and antagonized by the Lefty and Cerberus families of secreted factors [3].
  • Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development [4].
  • Here we test whether Lefty1 is a direct target of Oct3/4 [5].
  • We identified an ES cell-specific enhancer upstream of the Lefty1 promoter that contains binding sites for Oct3/4 and Sox2 [5].
  • Here, we show that Nodal and Furin are initially co-expressed in the primitive endoderm together with a subset of DVE markers such as Lefty1 and Hex [6].

Biological context of LEFTY1


Anatomical context of LEFTY1

  • In contrast to mouse lefty1, which is expressed predominantly in the floor plate under the control of a right side-specific silencer, human LEFTY1 is expressed mainly in left lateral plate mesoderm under the control of an ASE-like left side-specific enhancer [7].
  • Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3 [10].
  • Expression analysis indicates that the early expression of nodal, BMP2/4 and lefty is restricted to the oral ectoderm reflecting their role in providing positional information along the oral-aboral axis of the embryo [11].
  • Furthermore, adding lefty-1, a nodal antagonist, to the blastoderm inhibited the expression of SMA, and nodal plus BMP antagonist up-regulated the expression of SMA in cultured posterior epiblast [12].

Associations of LEFTY1 with chemical compounds

  • In this model, Lefty is regulated by the dose of doxycycline [1].
  • To drive the expression of Lefty, we have placed Lefty under control of a tetracycline-responsive promoter which responds to a sequence variant of the reversed tet transcriptional activator (rtTA), rtTA2S-M2 [1].

Regulatory relationships of LEFTY1

  • Moreover, lefty inhibits CTGF and collagen mRNA synthesis and increases collagenolysis and elastolysis and as a result of these actions, lefty significantly reduces the amount of collagen deposited in tissues [13].
  • Here, we show that TGF-beta signaling is inhibited by lefty, a novel member of the TGF-beta superfamily [8].

Other interactions of LEFTY1


Analytical, diagnostic and therapeutic context of LEFTY1


  1. Tet responsive and adenovirus based constructs for regulated in vivo expression of Lefty. Mikhailik, A., Tang, M., Hearing, P., Ravishankar, V., Tabibzadeh, S. Front. Biosci. (2006) [Pubmed]
  2. Role of EBAF/Lefty in implantation and uterine bleeding. Tabibzadeh, S. Ernst Schering Res. Found. Workshop (2005) [Pubmed]
  3. Nodal signaling in vertebrate development. Schier, A.F. Annu. Rev. Cell Dev. Biol. (2003) [Pubmed]
  4. Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development. Kosaki, K., Bassi, M.T., Kosaki, R., Lewin, M., Belmont, J., Schauer, G., Casey, B. Am. J. Hum. Genet. (1999) [Pubmed]
  5. Klf4 cooperates with oct3/4 and sox2 to activate the lefty1 core promoter in embryonic stem cells. Nakatake, Y., Fukui, N., Iwamatsu, Y., Masui, S., Takahashi, K., Yagi, R., Yagi, K., Miyazaki, J., Matoba, R., Ko, M.S., Niwa, H. Mol. Cell. Biol. (2006) [Pubmed]
  6. 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]
  7. Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes. Yashiro, K., Saijoh, Y., Sakuma, R., Tada, M., Tomita, N., Amano, K., Matsuda, Y., Monden, M., Okada, S., Hamada, H. Genes Cells (2000) [Pubmed]
  8. Lefty inhibits receptor-regulated Smad phosphorylation induced by the activated transforming growth factor-beta receptor. Ulloa, L., Tabibzadeh, S. J. Biol. Chem. (2001) [Pubmed]
  9. Nodal signaling: CrypticLefty mechanism of antagonism decoded. Branford, W.W., Yost, H.J. Curr. Biol. (2004) [Pubmed]
  10. 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]
  11. RTK and TGF-beta signaling pathways genes in the sea urchin genome. Lapraz, F., R??ttinger, E., Duboc, V., Range, R., Duloquin, L., Walton, K., Wu, S.Y., Bradham, C., Loza, M.A., Hibino, T., Wilson, K., Poustka, A., McClay, D., Angerer, L., Gache, C., Lepage, T. Dev. Biol. (2006) [Pubmed]
  12. Induction of initial cardiomyocyte alpha-actin--smooth muscle alpha-actin--in cultured avian pregastrula epiblast: a role for nodal and BMP antagonist. Matsui, H., Ikeda, K., Nakatani, K., Sakabe, M., Yamagishi, T., Nakanishi, T., Nakajima, Y. Dev. Dyn. (2005) [Pubmed]
  13. Homeostasis of extracellular matrix by TGF-beta and lefty. Tabibzadeh, S. Front. Biosci. (2002) [Pubmed]
  14. Lefty at the crossroads of "stemness" and differentiative events. Tabibzadeh, S., Hemmati-Brivanlou, A. Stem Cells (2006) [Pubmed]
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